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  • Articles  (154)
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  • Articles  (154)
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  • American Association for the Advancement of Science (AAAS)  (154)
  • American Institute of Physics (AIP)
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  • 1
    Publication Date: 2012-02-22
    Description: The lyso-phospholipid sphingosine 1-phosphate modulates lymphocyte trafficking, endothelial development and integrity, heart rate, and vascular tone and maturation by activating G protein-coupled sphingosine 1-phosphate receptors. Here, we present the crystal structure of the sphingosine 1-phosphate receptor 1 fused to T4-lysozyme (S1P(1)-T4L) in complex with an antagonist sphingolipid mimic. Extracellular access to the binding pocket is occluded by the amino terminus and extracellular loops of the receptor. Access is gained by ligands entering laterally between helices I and VII within the transmembrane region of the receptor. This structure, along with mutagenesis, agonist structure-activity relationship data, and modeling, provides a detailed view of the molecular recognition and requirement for hydrophobic volume that activates S1P(1), resulting in the modulation of immune and stromal cell responses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338336/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338336/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hanson, Michael A -- Roth, Christopher B -- Jo, Euijung -- Griffith, Mark T -- Scott, Fiona L -- Reinhart, Greg -- Desale, Hans -- Clemons, Bryan -- Cahalan, Stuart M -- Schuerer, Stephan C -- Sanna, M Germana -- Han, Gye Won -- Kuhn, Peter -- Rosen, Hugh -- Stevens, Raymond C -- AI055509/AI/NIAID NIH HHS/ -- AI074564/AI/NIAID NIH HHS/ -- P50 GM073197/GM/NIGMS NIH HHS/ -- P50 GM073197-08/GM/NIGMS NIH HHS/ -- R01 AI055509/AI/NIAID NIH HHS/ -- R01 AI055509-04/AI/NIAID NIH HHS/ -- U01 AI074564/AI/NIAID NIH HHS/ -- U01 AI074564-04/AI/NIAID NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- U54 GM094618-02/GM/NIGMS NIH HHS/ -- U54 MH084512/MH/NIMH NIH HHS/ -- U54 MH084512-04/MH/NIMH NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Feb 17;335(6070):851-5. doi: 10.1126/science.1215904.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Receptos, 10835 Road to the Cure, San Diego, CA 92121, USA. mhanson@receptos.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22344443" target="_blank"〉PubMed〈/a〉
    Keywords: Anilides/chemistry ; Binding Sites ; Crystallography, X-Ray ; Models, Molecular ; Muramidase/chemistry ; Mutagenesis ; Organophosphonates/chemistry ; Protein Conformation ; Receptors, Lysosphingolipid/agonists/antagonists & inhibitors/*chemistry/genetics ; Recombinant Fusion Proteins/chemistry/genetics
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  • 2
    Publication Date: 2012-04-21
    Description: Prion conversion from a soluble protein to an aggregated state may be involved in the cellular adaptation of yeast to the environment. However, it remains unclear whether and how cells actively use prion conversion to acquire a fitness advantage in response to environmental stress. We identified Mod5, a yeast transfer RNA isopentenyltransferase lacking glutamine/asparagine-rich domains, as a yeast prion protein and found that its prion conversion in yeast regulated the sterol biosynthetic pathway for acquired cellular resistance against antifungal agents. Furthermore, selective pressure by antifungal drugs on yeast facilitated the de novo appearance of Mod5 prion states for cell survival. Thus, phenotypic changes caused by active prion conversion under environmental selection may contribute to cellular adaptation in living organisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suzuki, Genjiro -- Shimazu, Naoyuki -- Tanaka, Motomasa -- New York, N.Y. -- Science. 2012 Apr 20;336(6079):355-9. doi: 10.1126/science.1219491.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Protein Conformation Diseases, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22517861" target="_blank"〉PubMed〈/a〉
    Keywords: Alkyl and Aryl Transferases/*chemistry/genetics/*metabolism ; Antifungal Agents/*pharmacology ; Biosynthetic Pathways ; Crosses, Genetic ; Drug Resistance, Fungal ; Ergosterol/biosynthesis ; Fluorouracil/pharmacology ; Microbial Viability ; Prions/*chemistry/genetics/metabolism ; Protein Conformation ; Protein Structure, Tertiary ; RNA, Fungal/metabolism ; RNA, Transfer/metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Saccharomyces cerevisiae/chemistry/*drug effects/genetics/*physiology ; Saccharomyces cerevisiae Proteins/*chemistry/genetics/*metabolism ; Selection, Genetic ; Solubility ; *Stress, Physiological
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  • 3
    Publication Date: 2012-04-21
    Description: Salicylate, a plant product, has been in medicinal use since ancient times. More recently, it has been replaced by synthetic derivatives such as aspirin and salsalate, both of which are rapidly broken down to salicylate in vivo. At concentrations reached in plasma after administration of salsalate or of aspirin at high doses, salicylate activates adenosine monophosphate-activated protein kinase (AMPK), a central regulator of cell growth and metabolism. Salicylate binds at the same site as the synthetic activator A-769662 to cause allosteric activation and inhibition of dephosphorylation of the activating phosphorylation site, threonine-172. In AMPK knockout mice, effects of salicylate to increase fat utilization and to lower plasma fatty acids in vivo were lost. Our results suggest that AMPK activation could explain some beneficial effects of salsalate and aspirin in humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399766/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399766/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hawley, Simon A -- Fullerton, Morgan D -- Ross, Fiona A -- Schertzer, Jonathan D -- Chevtzoff, Cyrille -- Walker, Katherine J -- Peggie, Mark W -- Zibrova, Darya -- Green, Kevin A -- Mustard, Kirsty J -- Kemp, Bruce E -- Sakamoto, Kei -- Steinberg, Gregory R -- Hardie, D Grahame -- 080982/Wellcome Trust/United Kingdom -- 097726/Wellcome Trust/United Kingdom -- MC_U127088492/Medical Research Council/United Kingdom -- Canadian Institutes of Health Research/Canada -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2012 May 18;336(6083):918-22. doi: 10.1126/science.1215327. Epub 2012 Apr 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22517326" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/genetics/*metabolism ; Amino Acid Substitution ; Animals ; Aspirin/pharmacology ; Binding Sites ; Carbohydrate Metabolism/drug effects ; Cell Line ; Enzyme Activation ; Enzyme Activators/pharmacology ; HEK293 Cells ; Humans ; Lipid Metabolism/drug effects ; Liver/drug effects/metabolism ; Mice ; Mice, Knockout ; Mutation ; Oxygen Consumption/drug effects ; Phosphorylation ; Pyrones/pharmacology ; Rats ; Salicylates/blood/*metabolism/*pharmacology ; Thiophenes/pharmacology
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  • 4
    Publication Date: 2012-09-29
    Description: Most living species exploit a limited range of resources. However, little is known about how tight associations build up during evolution between such specialist species and the hosts they use. We examined the dependence of Drosophila pachea on its single host, the senita cactus. Several amino acid changes in the Neverland oxygenase rendered D. pachea unable to transform cholesterol into 7-dehydrocholesterol (the first reaction in the steroid hormone biosynthetic pathway in insects) and thus made D. pachea dependent on the uncommon sterols of its host plant. The neverland mutations increase survival on the cactus's unusual sterols and are in a genomic region that faced recent positive selection. This study illustrates how relatively few genetic changes in a single gene may restrict the ecological niche of a species.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729188/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729188/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lang, Michael -- Murat, Sophie -- Clark, Andrew G -- Gouppil, Geraldine -- Blais, Catherine -- Matzkin, Luciano M -- Guittard, Emilie -- Yoshiyama-Yanagawa, Takuji -- Kataoka, Hiroshi -- Niwa, Ryusuke -- Lafont, Rene -- Dauphin-Villemant, Chantal -- Orgogozo, Virginie -- AI064950/AI/NIAID NIH HHS/ -- R01 AI064950/AI/NIAID NIH HHS/ -- R01 HG003229/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2012 Sep 28;337(6102):1658-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CNRS UMR7592, Universite Paris Diderot, Sorbonne Paris Cite, Institut Jacques Monod, Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23019649" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cactaceae/*metabolism ; Cholesterol/metabolism ; Conserved Sequence ; Dehydrocholesterols/metabolism ; Drosophila/genetics/*physiology ; Drosophila Proteins/chemistry/*genetics/metabolism ; *Food Chain ; Molecular Sequence Data ; *Mutation ; Oxygenases/chemistry/*genetics/metabolism ; Protein Conformation ; RNA Interference ; Selection, Genetic ; Species Specificity
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  • 5
    Publication Date: 2012-06-02
    Description: Cellular membrane fusion is thought to proceed through intermediates including docking of apposed lipid bilayers, merging of proximal leaflets to form a hemifusion diaphragm, and fusion pore opening. A membrane-bridging four-helix complex of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) mediates fusion. However, how assembly of the SNARE complex generates docking and other fusion intermediates is unknown. Using a cell-free reaction, we identified intermediates visually and then arrested the SNARE fusion machinery when fusion was about to begin. Partial and directional assembly of SNAREs tightly docked bilayers, but efficient fusion and an extended form of hemifusion required assembly beyond the core complex to the membrane-connecting linkers. We propose that straining of lipids at the edges of an extended docking zone initiates fusion.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3677693/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3677693/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hernandez, Javier M -- Stein, Alexander -- Behrmann, Elmar -- Riedel, Dietmar -- Cypionka, Anna -- Farsi, Zohreh -- Walla, Peter J -- Raunser, Stefan -- Jahn, Reinhard -- 3P01GM072694-05S1/GM/NIGMS NIH HHS/ -- P01 GM072694/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Jun 22;336(6088):1581-4. doi: 10.1126/science.1221976. Epub 2012 May 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22653732" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Lipid Bilayers/chemistry/*metabolism ; *Liposomes/chemistry/metabolism ; *Membrane Fusion ; Protein Binding ; Protein Conformation ; Rats ; SNARE Proteins/chemistry/*metabolism ; Vesicle-Associated Membrane Protein 2/metabolism
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  • 6
    Publication Date: 2012-09-22
    Description: Cytoplasmic dynein is a microtubule-based motor required for intracellular transport and cell division. Its movement involves coupling cycles of track binding and release with cycles of force-generating nucleotide hydrolysis. How this is accomplished given the ~25 nanometers separating dynein's track- and nucleotide-binding sites is not understood. Here, we present a subnanometer-resolution structure of dynein's microtubule-binding domain bound to microtubules by cryo-electron microscopy that was used to generate a pseudo-atomic model of the complex with molecular dynamics. We identified large rearrangements triggered by track binding and specific interactions, confirmed by mutagenesis and single-molecule motility assays, which tune dynein's affinity for microtubules. Our results provide a molecular model for how dynein's binding to microtubules is communicated to the rest of the motor.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919166/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919166/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Redwine, William B -- Hernandez-Lopez, Rogelio -- Zou, Sirui -- Huang, Julie -- Reck-Peterson, Samara L -- Leschziner, Andres E -- 1 DP2 OD004268-1/OD/NIH HHS/ -- DP2 OD004268/OD/NIH HHS/ -- New York, N.Y. -- Science. 2012 Sep 21;337(6101):1532-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22997337" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Binding Sites ; Cryoelectron Microscopy ; Cytoplasmic Dyneins/*chemistry/metabolism ; Hydrogen Bonding ; Microtubules/*metabolism ; Models, Molecular ; Molecular Dynamics Simulation ; Mutagenesis ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism
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  • 7
    Publication Date: 2012-05-15
    Description: Poly(ADP-ribose) polymerase-1 (PARP-1) (ADP, adenosine diphosphate) has a modular domain architecture that couples DNA damage detection to poly(ADP-ribosyl)ation activity through a poorly understood mechanism. Here, we report the crystal structure of a DNA double-strand break in complex with human PARP-1 domains essential for activation (Zn1, Zn3, WGR-CAT). PARP-1 engages DNA as a monomer, and the interaction with DNA damage organizes PARP-1 domains into a collapsed conformation that can explain the strong preference for automodification. The Zn1, Zn3, and WGR domains collectively bind to DNA, forming a network of interdomain contacts that links the DNA damage interface to the catalytic domain (CAT). The DNA damage-induced conformation of PARP-1 results in structural distortions that destabilize the CAT. Our results suggest that an increase in CAT protein dynamics underlies the DNA-dependent activation mechanism of PARP-1.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532513/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532513/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Langelier, Marie-France -- Planck, Jamie L -- Roy, Swati -- Pascal, John M -- P30 EB009998/EB/NIBIB NIH HHS/ -- P30CA56036/CA/NCI NIH HHS/ -- R01 GM087282/GM/NIGMS NIH HHS/ -- R01087282/PHS HHS/ -- New York, N.Y. -- Science. 2012 May 11;336(6082):728-32. doi: 10.1126/science.1216338.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, The Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22582261" target="_blank"〉PubMed〈/a〉
    Keywords: Catalytic Domain ; Crystallography, X-Ray ; DNA/*chemistry/*metabolism ; *DNA Breaks, Double-Stranded ; Enzyme Stability ; Humans ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Nucleic Acid Conformation ; Poly Adenosine Diphosphate Ribose/*metabolism ; Poly(ADP-ribose) Polymerases/*chemistry/*metabolism ; Protein Binding ; Protein Conformation ; Protein Structure, Tertiary
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  • 8
    Publication Date: 2012-09-18
    Description: The identification of proximate amino acids by chemical cross-linking and mass spectrometry (XL-MS) facilitates the structural analysis of homogeneous protein complexes. We gained distance restraints on a modular interaction network of protein complexes affinity-purified from human cells by applying an adapted XL-MS protocol. Systematic analysis of human protein phosphatase 2A (PP2A) complexes identified 176 interprotein and 570 intraprotein cross-links that link specific trimeric PP2A complexes to a multitude of adaptor proteins that control their cellular functions. Spatial restraints guided molecular modeling of the binding interface between immunoglobulin binding protein 1 (IGBP1) and PP2A and revealed the topology of TCP1 ring complex (TRiC) chaperonin interacting with the PP2A regulatory subunit 2ABG. This study establishes XL-MS as an integral part of hybrid structural biology approaches for the analysis of endogenous protein complexes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herzog, Franz -- Kahraman, Abdullah -- Boehringer, Daniel -- Mak, Raymond -- Bracher, Andreas -- Walzthoeni, Thomas -- Leitner, Alexander -- Beck, Martin -- Hartl, Franz-Ulrich -- Ban, Nenad -- Malmstrom, Lars -- Aebersold, Ruedi -- New York, N.Y. -- Science. 2012 Sep 14;337(6100):1348-52. doi: 10.1126/science.1221483.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Institute of Molecular Systems Biology, Eidgenossische Technische Hochschule Zurich, Wolfgang-Pauli Strasse 16, 8093 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22984071" target="_blank"〉PubMed〈/a〉
    Keywords: Chaperonins/chemistry ; Cross-Linking Reagents/chemistry ; Crystallography, X-Ray ; Humans ; Mass Spectrometry/*methods ; *Metabolic Networks and Pathways ; Protein Conformation ; Protein Interaction Mapping/*methods ; Protein Phosphatase 2/*chemistry
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  • 9
    Publication Date: 2012-08-11
    Description: Identification of broadly neutralizing antibodies against influenza A viruses has raised hopes for the development of monoclonal antibody-based immunotherapy and "universal" vaccines for influenza. However, a substantial part of the annual flu burden is caused by two cocirculating, antigenically distinct lineages of influenza B viruses. Here, we report human monoclonal antibodies, CR8033, CR8071, and CR9114, that protect mice against lethal challenge from both lineages. Antibodies CR8033 and CR8071 recognize distinct conserved epitopes in the head region of the influenza B hemagglutinin (HA), whereas CR9114 binds a conserved epitope in the HA stem and protects against lethal challenge with influenza A and B viruses. These antibodies may inform on development of monoclonal antibody-based treatments and a universal flu vaccine for all influenza A and B viruses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538841/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538841/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dreyfus, Cyrille -- Laursen, Nick S -- Kwaks, Ted -- Zuijdgeest, David -- Khayat, Reza -- Ekiert, Damian C -- Lee, Jeong Hyun -- Metlagel, Zoltan -- Bujny, Miriam V -- Jongeneelen, Mandy -- van der Vlugt, Remko -- Lamrani, Mohammed -- Korse, Hans J W M -- Geelen, Eric -- Sahin, Ozcan -- Sieuwerts, Martijn -- Brakenhoff, Just P J -- Vogels, Ronald -- Li, Olive T W -- Poon, Leo L M -- Peiris, Malik -- Koudstaal, Wouter -- Ward, Andrew B -- Wilson, Ian A -- Goudsmit, Jaap -- Friesen, Robert H E -- GM080209/GM/NIGMS NIH HHS/ -- P41RR001209/RR/NCRR NIH HHS/ -- RR017573/RR/NCRR NIH HHS/ -- T32 GM080209/GM/NIGMS NIH HHS/ -- U54 GM094586/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Sep 14;337(6100):1343-8. doi: 10.1126/science.1222908. Epub 2012 Aug 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22878502" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antibodies, Monoclonal/chemistry/*immunology ; Antibodies, Neutralizing/chemistry/immunology ; Conserved Sequence ; Hemagglutinin Glycoproteins, Influenza Virus/*immunology ; Humans ; Immunodominant Epitopes/chemistry/*immunology ; Influenza B virus/*immunology ; Influenza Vaccines/*immunology ; Mice ; Molecular Sequence Data ; Neutralization Tests ; Orthomyxoviridae Infections/*prevention & control ; Protein Conformation
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  • 10
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-12-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉New York, N.Y. -- Science. 2012 Dec 21;338(6114):1525-32. doi: 10.1126/science.338.6114.1525.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23258865" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain-Computer Interfaces ; Crystallography, X-Ray ; Elementary Particles ; Embryonic Stem Cells ; Fossils ; Genetic Engineering ; Genome, Human ; Genomics ; Hominidae/genetics ; Humans ; Lasers ; Mars ; Oocytes/cytology ; Protein Conformation ; Protozoan Proteins/chemistry ; *Science ; Sequence Analysis, DNA ; Spacecraft ; Trypanosoma brucei brucei/enzymology
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  • 11
    Publication Date: 2012-02-11
    Description: Sodium/calcium (Na(+)/Ca(2+)) exchangers (NCX) are membrane transporters that play an essential role in maintaining the homeostasis of cytosolic Ca(2+) for cell signaling. We demonstrated the Na(+)/Ca(2+)-exchange function of an NCX from Methanococcus jannaschii (NCX_Mj) and report its 1.9 angstrom crystal structure in an outward-facing conformation. Containing 10 transmembrane helices, the two halves of NCX_Mj share a similar structure with opposite orientation. Four ion-binding sites cluster at the center of the protein: one specific for Ca(2+) and three that likely bind Na(+). Two passageways allow for Na(+) and Ca(2+) access to the central ion-binding sites from the extracellular side. Based on the symmetry of NCX_Mj and its ability to catalyze bidirectional ion-exchange reactions, we propose a structure model for the inward-facing NCX_Mj.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liao, Jun -- Li, Hua -- Zeng, Weizhong -- Sauer, David B -- Belmares, Ricardo -- Jiang, Youxing -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Feb 10;335(6069):686-90. doi: 10.1126/science.1215759.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22323814" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Archaeal Proteins/*chemistry/metabolism ; Binding Sites ; Calcium/*metabolism ; Crystallization ; Crystallography, X-Ray ; Ion Transport ; Ligands ; Methanococcales/*chemistry/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Structure, Secondary ; Sodium/*metabolism ; Sodium-Calcium Exchanger/*chemistry/*metabolism
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  • 12
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-12-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cho, Adrian -- New York, N.Y. -- Science. 2012 Nov 30;338(6111):1136. doi: 10.1126/science.338.6111.1136.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23197505" target="_blank"〉PubMed〈/a〉
    Keywords: Cathepsins/*chemistry ; Crystallography, X-Ray/*methods ; Cysteine Proteases/*chemistry ; *Lasers ; Protein Conformation ; Protozoan Proteins/*chemistry ; Trypanosoma brucei brucei/*enzymology
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  • 13
    Publication Date: 2012-11-28
    Description: The plasma membrane protein Orai forms the pore of the calcium release-activated calcium (CRAC) channel and generates sustained cytosolic calcium signals when triggered by depletion of calcium from the endoplasmic reticulum. The crystal structure of Orai from Drosophila melanogaster, determined at 3.35 angstrom resolution, reveals that the calcium channel is composed of a hexameric assembly of Orai subunits arranged around a central ion pore. The pore traverses the membrane and extends into the cytosol. A ring of glutamate residues on its extracellular side forms the selectivity filter. A basic region near the intracellular side can bind anions that may stabilize the closed state. The architecture of the channel differs markedly from other ion channels and gives insight into the principles of selective calcium permeation and gating.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695727/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695727/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hou, Xiaowei -- Pedi, Leanne -- Diver, Melinda M -- Long, Stephen B -- GM094273/GM/NIGMS NIH HHS/ -- P30 CA008748/CA/NCI NIH HHS/ -- R01 GM094273/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Dec 7;338(6112):1308-13. doi: 10.1126/science.1228757. Epub 2012 Nov 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23180775" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Calcium/*chemistry ; Calcium Channels/*chemistry ; Crystallography, X-Ray ; Drosophila Proteins/agonists/*chemistry ; Glutamic Acid/chemistry ; Membrane Proteins/agonists/*chemistry ; Porosity ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary
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  • 14
    Publication Date: 2012-05-26
    Description: Transport between compartments of eukaryotic cells is mediated by coated vesicles. The archetypal protein coats COPI, COPII, and clathrin are conserved from yeast to human. Structural studies of COPII and clathrin coats assembled in vitro without membranes suggest that coat components assemble regular cages with the same set of interactions between components. Detailed three-dimensional structures of coated membrane vesicles have not been obtained. Here, we solved the structures of individual COPI-coated membrane vesicles by cryoelectron tomography and subtomogram averaging of in vitro reconstituted budding reactions. The coat protein complex, coatomer, was observed to adopt alternative conformations to change the number of other coatomers with which it interacts and to form vesicles with variable sizes and shapes. This represents a fundamentally different basis for vesicle coat assembly.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Faini, Marco -- Prinz, Simone -- Beck, Rainer -- Schorb, Martin -- Riches, James D -- Bacia, Kirsten -- Brugger, Britta -- Wieland, Felix T -- Briggs, John A G -- New York, N.Y. -- Science. 2012 Jun 15;336(6087):1451-4. doi: 10.1126/science.1221443. Epub 2012 May 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22628556" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; COP-Coated Vesicles/*chemistry/*ultrastructure ; Coat Protein Complex I/*chemistry ; Coatomer Protein/*chemistry ; Cryoelectron Microscopy ; Electron Microscope Tomography ; Image Processing, Computer-Assisted ; Mice ; Models, Molecular ; Protein Conformation
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  • 15
    Publication Date: 2012-03-17
    Description: In bacteria, ribosomes stalled at the end of truncated messages are rescued by transfer-messenger RNA (tmRNA), a bifunctional molecule that acts as both a transfer RNA (tRNA) and a messenger RNA (mRNA), and SmpB, a small protein that works in concert with tmRNA. Here, we present the crystal structure of a tmRNA fragment, SmpB and elongation factor Tu bound to the ribosome at 3.2 angstroms resolution. The structure shows how SmpB plays the role of both the anticodon loop of tRNA and portions of mRNA to facilitate decoding in the absence of an mRNA codon in the A site of the ribosome and explains why the tmRNA-SmpB system does not interfere with normal translation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763467/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763467/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neubauer, Cajetan -- Gillet, Reynald -- Kelley, Ann C -- Ramakrishnan, V -- 082086/Wellcome Trust/United Kingdom -- 096570/Wellcome Trust/United Kingdom -- MC_U105184332/Medical Research Council/United Kingdom -- U105184332/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2012 Mar 16;335(6074):1366-9. doi: 10.1126/science.1217039.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22422985" target="_blank"〉PubMed〈/a〉
    Keywords: Anticodon ; Bacterial Proteins/chemistry/metabolism ; Base Sequence ; Crystallography, X-Ray ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Peptide Elongation Factor Tu/*chemistry/metabolism ; Protein Biosynthesis ; Protein Conformation ; RNA, Bacterial/*chemistry/*metabolism ; RNA, Messenger/chemistry/metabolism ; RNA, Transfer/chemistry/metabolism ; RNA-Binding Proteins/*chemistry/*metabolism ; Ribosome Subunits, Small, Bacterial/chemistry/metabolism/ultrastructure ; Ribosomes/*chemistry/*metabolism/ultrastructure ; Thermus thermophilus/*chemistry/genetics/metabolism/ultrastructure
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  • 16
    Publication Date: 2012-04-21
    Description: Protein-folding intermediates have been implicated in amyloid fibril formation involved in neurodegenerative disorders. However, the structural mechanisms by which intermediates initiate fibrillar aggregation have remained largely elusive. To gain insight, we used relaxation dispersion nuclear magnetic resonance spectroscopy to determine the structure of a low-populated, on-pathway folding intermediate of the A39V/N53P/V55L (A, Ala; V, Val; N, Asn; P, Pro; L, Leu) Fyn SH3 domain. The carboxyl terminus remains disordered in this intermediate, thereby exposing the aggregation-prone amino-terminal beta strand. Accordingly, mutants lacking the carboxyl terminus and thus mimicking the intermediate fail to safeguard the folding route and spontaneously form fibrillar aggregates. The structure provides a detailed characterization of the non-native interactions stabilizing an aggregation-prone intermediate under native conditions and insight into how such an intermediate can derail folding and initiate fibrillation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neudecker, Philipp -- Robustelli, Paul -- Cavalli, Andrea -- Walsh, Patrick -- Lundstrom, Patrik -- Zarrine-Afsar, Arash -- Sharpe, Simon -- Vendruscolo, Michele -- Kay, Lewis E -- 089703/Wellcome Trust/United Kingdom -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2012 Apr 20;336(6079):362-6. doi: 10.1126/science.1214203.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22517863" target="_blank"〉PubMed〈/a〉
    Keywords: Amyloid/*chemistry ; Animals ; Chickens ; Hydrogen Bonding ; Models, Molecular ; Molecular Dynamics Simulation ; Mutant Proteins/chemistry ; Nuclear Magnetic Resonance, Biomolecular ; Protein Conformation ; *Protein Folding ; Protein Structure, Secondary ; Proto-Oncogene Proteins c-fyn/*chemistry/genetics ; Thermodynamics ; *src Homology Domains
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  • 17
    Publication Date: 2012-11-28
    Description: The influenza viruses cause annual epidemics of respiratory disease and occasional pandemics, which constitute a major public-health issue. The segmented negative-stranded RNAs are associated with the polymerase complex and nucleoprotein (NP), forming ribonucleoproteins (RNPs), which are responsible for virus transcription and replication. We describe the structure of native RNPs derived from virions. They show a double-helical conformation in which two NP strands of opposite polarity are associated with each other along the helix. Both strands are connected by a short loop at one end of the particle and interact with the polymerase complex at the other end. This structure will be relevant for unraveling the mechanisms of nuclear import of parental virus RNPs, their transcription and replication, and the encapsidation of progeny RNPs into virions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arranz, Rocio -- Coloma, Rocio -- Chichon, Francisco Javier -- Conesa, Jose Javier -- Carrascosa, Jose L -- Valpuesta, Jose M -- Ortin, Juan -- Martin-Benito, Jaime -- New York, N.Y. -- Science. 2012 Dec 21;338(6114):1634-7. doi: 10.1126/science.1228172. Epub 2012 Nov 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Macromolecular Structure, Centro Nacional de Biotecnologia [Consejo Superior de Investigaciones Cienficas (CSIC)], Madrid, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23180776" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Nucleus/metabolism/virology ; Cryoelectron Microscopy ; Electron Microscope Tomography ; Image Processing, Computer-Assisted ; Influenza A Virus, H1N1 Subtype/*chemistry/physiology/ultrastructure ; Madin Darby Canine Kidney Cells ; Microscopy, Electron ; Models, Molecular ; Protein Conformation ; Protein Structure, Secondary ; RNA Replicase/chemistry/metabolism/ultrastructure ; RNA, Viral/*chemistry/metabolism ; RNA-Binding Proteins/chemistry/metabolism/ultrastructure ; Ribonucleoproteins/*chemistry/metabolism/ultrastructure ; Transcription, Genetic ; Viral Core Proteins/chemistry/metabolism/ultrastructure ; Viral Proteins/*chemistry/metabolism/ultrastructure ; Virion/*chemistry/ultrastructure
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  • 18
    Publication Date: 2012-03-03
    Description: Bacteria adapt to environmental stimuli by adjusting their transcriptomes in a complex manner, the full potential of which has yet to be established for any individual bacterial species. Here, we report the transcriptomes of Bacillus subtilis exposed to a wide range of environmental and nutritional conditions that the organism might encounter in nature. We comprehensively mapped transcription units (TUs) and grouped 2935 promoters into regulons controlled by various RNA polymerase sigma factors, accounting for ~66% of the observed variance in transcriptional activity. This global classification of promoters and detailed description of TUs revealed that a large proportion of the detected antisense RNAs arose from potentially spurious transcription initiation by alternative sigma factors and from imperfect control of transcription termination.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nicolas, Pierre -- Mader, Ulrike -- Dervyn, Etienne -- Rochat, Tatiana -- Leduc, Aurelie -- Pigeonneau, Nathalie -- Bidnenko, Elena -- Marchadier, Elodie -- Hoebeke, Mark -- Aymerich, Stephane -- Becher, Dorte -- Bisicchia, Paola -- Botella, Eric -- Delumeau, Olivier -- Doherty, Geoff -- Denham, Emma L -- Fogg, Mark J -- Fromion, Vincent -- Goelzer, Anne -- Hansen, Annette -- Hartig, Elisabeth -- Harwood, Colin R -- Homuth, Georg -- Jarmer, Hanne -- Jules, Matthieu -- Klipp, Edda -- Le Chat, Ludovic -- Lecointe, Francois -- Lewis, Peter -- Liebermeister, Wolfram -- March, Anika -- Mars, Ruben A T -- Nannapaneni, Priyanka -- Noone, David -- Pohl, Susanne -- Rinn, Bernd -- Rugheimer, Frank -- Sappa, Praveen K -- Samson, Franck -- Schaffer, Marc -- Schwikowski, Benno -- Steil, Leif -- Stulke, Jorg -- Wiegert, Thomas -- Devine, Kevin M -- Wilkinson, Anthony J -- van Dijl, Jan Maarten -- Hecker, Michael -- Volker, Uwe -- Bessieres, Philippe -- Noirot, Philippe -- New York, N.Y. -- Science. 2012 Mar 2;335(6072):1103-6. doi: 10.1126/science.1206848.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INRA, UR1077, Mathematique Informatique et Genome, Jouy-en-Josas, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22383849" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Algorithms ; Bacillus subtilis/*genetics/*physiology ; Binding Sites ; Gene Expression Profiling ; *Gene Expression Regulation, Bacterial ; Gene Regulatory Networks ; Oligonucleotide Array Sequence Analysis ; *Promoter Regions, Genetic ; RNA, Antisense/genetics/metabolism ; RNA, Bacterial/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Regulon ; Sigma Factor/metabolism ; Terminator Regions, Genetic ; *Transcription, Genetic ; *Transcriptome
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  • 19
    Publication Date: 2012-01-24
    Description: Extracellular ligand binding to G protein-coupled receptors (GPCRs) modulates G protein and beta-arrestin signaling by changing the conformational states of the cytoplasmic region of the receptor. Using site-specific (19)F-NMR (fluorine-19 nuclear magnetic resonance) labels in the beta(2)-adrenergic receptor (beta(2)AR) in complexes with various ligands, we observed that the cytoplasmic ends of helices VI and VII adopt two major conformational states. Changes in the NMR signals reveal that agonist binding primarily shifts the equilibrium toward the G protein-specific active state of helix VI. In contrast, beta-arrestin-biased ligands predominantly impact the conformational states of helix VII. The selective effects of different ligands on the conformational equilibria involving helices VI and VII provide insights into the long-range structural plasticity of beta(2)AR in partial and biased agonist signaling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292700/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292700/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Jeffrey J -- Horst, Reto -- Katritch, Vsevolod -- Stevens, Raymond C -- Wuthrich, Kurt -- P50 GM073197/GM/NIGMS NIH HHS/ -- P50 GM073197-08/GM/NIGMS NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- U54 GM094618-02/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Mar 2;335(6072):1106-10. doi: 10.1126/science.1215802. Epub 2012 Jan 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22267580" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic beta-2 Receptor Agonists/chemistry/*metabolism/pharmacology ; Arrestins/metabolism ; Binding Sites ; Carbazoles/chemistry/metabolism/pharmacology ; Cytoplasm/chemistry ; Drug Partial Agonism ; Fluorine ; Isoetharine/chemistry/metabolism/pharmacology ; Isoproterenol/metabolism ; Ligands ; Models, Molecular ; Nuclear Magnetic Resonance, Biomolecular ; Propanolamines/chemistry/metabolism/pharmacology ; Protein Conformation ; Protein Structure, Secondary ; Receptors, Adrenergic, beta-2/*chemistry/*metabolism ; *Signal Transduction ; Structure-Activity Relationship
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  • 20
    Publication Date: 2012-08-21
    Description: Stu2p/XMAP215/Dis1 family proteins are evolutionarily conserved regulatory factors that use alphabeta-tubulin-interacting tumor overexpressed gene (TOG) domains to catalyze fast microtubule growth. Catalysis requires that these polymerases discriminate between unpolymerized and polymerized forms of alphabeta-tubulin, but the mechanism by which they do so has remained unclear. Here, we report the structure of the TOG1 domain from Stu2p bound to yeast alphabeta-tubulin. TOG1 binds alphabeta-tubulin in a way that excludes equivalent binding of a second TOG domain. Furthermore, TOG1 preferentially binds a curved conformation of alphabeta-tubulin that cannot be incorporated into microtubules, contacting alpha- and beta-tubulin surfaces that do not participate in microtubule assembly. Conformation-selective interactions with alphabeta-tubulin explain how TOG-containing polymerases discriminate between unpolymerized and polymerized forms of alphabeta-tubulin and how they selectively recognize the growing end of the microtubule.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3734851/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3734851/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ayaz, Pelin -- Ye, Xuecheng -- Huddleston, Patrick -- Brautigam, Chad A -- Rice, Luke M -- GM-098543/GM/NIGMS NIH HHS/ -- R01 GM098543/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Aug 17;337(6096):857-60. doi: 10.1126/science.1221698.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22904013" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Gene Expression Regulation, Neoplastic ; Genes, Neoplasm ; Microtubule-Associated Proteins/*chemistry/genetics ; Microtubules/*enzymology ; Polymerization ; Protein Conformation ; Protein Structure, Tertiary ; Saccharomyces cerevisiae Proteins/*chemistry/genetics ; Tubulin/*chemistry
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  • 21
    Publication Date: 2012-06-02
    Description: Pattern recognition receptors confer plant resistance to pathogen infection by recognizing the conserved pathogen-associated molecular patterns. The cell surface receptor chitin elicitor receptor kinase 1 of Arabidopsis (AtCERK1) directly binds chitin through its lysine motif (LysM)-containing ectodomain (AtCERK1-ECD) to activate immune responses. The crystal structure that we solved of an AtCERK1-ECD complexed with a chitin pentamer reveals that their interaction is primarily mediated by a LysM and three chitin residues. By acting as a bivalent ligand, a chitin octamer induces AtCERK1-ECD dimerization that is inhibited by shorter chitin oligomers. A mutation attenuating chitin-induced AtCERK1-ECD dimerization or formation of nonproductive AtCERK1 dimer by overexpression of AtCERK1-ECD compromises AtCERK1-mediated signaling in plant cells. Together, our data support the notion that chitin-induced AtCERK1 dimerization is critical for its activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Tingting -- Liu, Zixu -- Song, Chuanjun -- Hu, Yunfei -- Han, Zhifu -- She, Ji -- Fan, Fangfang -- Wang, Jiawei -- Jin, Changwen -- Chang, Junbiao -- Zhou, Jian-Min -- Chai, Jijie -- New York, N.Y. -- Science. 2012 Jun 1;336(6085):1160-4. doi: 10.1126/science.1218867.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate Program in Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22654057" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylglucosamine/chemistry/metabolism ; Amino Acid Motifs ; Amino Acid Sequence ; Arabidopsis/immunology/*metabolism ; Arabidopsis Proteins/*chemistry/genetics/*metabolism ; Binding Sites ; Chitin/chemistry/*metabolism ; Crystallography, X-Ray ; Hydrogen Bonding ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/chemistry/metabolism ; Phosphorylation ; Plants, Genetically Modified ; Protein Multimerization ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/*chemistry/genetics/*metabolism ; Receptors, Pattern Recognition/*chemistry/genetics/*metabolism ; Signal Transduction
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  • 22
    Publication Date: 2012-04-14
    Description: The mechanism of ion channel voltage gating-how channels open and close in response to voltage changes-has been debated since Hodgkin and Huxley's seminal discovery that the crux of nerve conduction is ion flow across cellular membranes. Using all-atom molecular dynamics simulations, we show how a voltage-gated potassium channel (KV) switches between activated and deactivated states. On deactivation, pore hydrophobic collapse rapidly halts ion flow. Subsequent voltage-sensing domain (VSD) relaxation, including inward, 15-angstrom S4-helix motion, completes the transition. On activation, outward S4 motion tightens the VSD-pore linker, perturbing linker-S6-helix packing. Fluctuations allow water, then potassium ions, to reenter the pore; linker-S6 repacking stabilizes the open pore. We propose a mechanistic model for the sodium/potassium/calcium voltage-gated ion channel superfamily that reconciles apparently conflicting experimental data.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jensen, Morten O -- Jogini, Vishwanath -- Borhani, David W -- Leffler, Abba E -- Dror, Ron O -- Shaw, David E -- New York, N.Y. -- Science. 2012 Apr 13;336(6078):229-33. doi: 10.1126/science.1216533.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉D E Shaw Research, New York, NY 10036, USA. morten.jensen@DEShawResearch.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22499946" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Hydrophobic and Hydrophilic Interactions ; *Ion Channel Gating ; Kv1.2 Potassium Channel/*chemistry/*metabolism ; Membrane Potentials ; Models, Biological ; Models, Molecular ; Molecular Dynamics Simulation ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Rats ; Recombinant Fusion Proteins/chemistry/metabolism ; Shab Potassium Channels/*chemistry/*metabolism
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  • 23
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-11-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schubeler, Dirk -- New York, N.Y. -- Science. 2012 Nov 9;338(6108):756-7. doi: 10.1126/science.1227243.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland. dirk@fmi.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23139324" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; *CpG Islands ; *DNA Methylation ; DNA-Binding Proteins/metabolism ; Enhancer Elements, Genetic ; *Epigenesis, Genetic ; *Gene Expression Regulation ; Humans ; Promoter Regions, Genetic ; Transcription Factors/metabolism
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  • 24
    Publication Date: 2012-02-11
    Description: The recently identified plant photoreceptor UVR8 (UV RESISTANCE LOCUS 8) triggers regulatory changes in gene expression in response to ultraviolet-B (UV-B) light through an unknown mechanism. Here, crystallographic and solution structures of the UVR8 homodimer, together with mutagenesis and far-UV circular dichroism spectroscopy, reveal its mechanisms for UV-B perception and signal transduction. beta-propeller subunits form a remarkable, tryptophan-dominated, dimer interface stitched together by a complex salt-bridge network. Salt-bridging arginines flank the excitonically coupled cross-dimer tryptophan "pyramid" responsible for UV-B sensing. Photoreception reversibly disrupts salt bridges, triggering dimer dissociation and signal initiation. Mutation of a single tryptophan to phenylalanine retunes the photoreceptor to detect UV-C wavelengths. Our analyses establish how UVR8 functions as a photoreceptor without a prosthetic chromophore to promote plant development and survival in sunlight.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3505452/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3505452/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Christie, John M -- Arvai, Andrew S -- Baxter, Katherine J -- Heilmann, Monika -- Pratt, Ashley J -- O'Hara, Andrew -- Kelly, Sharon M -- Hothorn, Michael -- Smith, Brian O -- Hitomi, Kenichi -- Jenkins, Gareth I -- Getzoff, Elizabeth D -- GM37684/GM/NIGMS NIH HHS/ -- R01 GM037684/GM/NIGMS NIH HHS/ -- Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2012 Mar 23;335(6075):1492-6. doi: 10.1126/science.1218091. Epub 2012 Feb 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22323738" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/physiology ; Arabidopsis Proteins/*chemistry/genetics/*metabolism ; Arginine/chemistry ; Chromosomal Proteins, Non-Histone/*chemistry/genetics/*metabolism ; Circular Dichroism ; Crystallography, X-Ray ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Light Signal Transduction ; Models, Molecular ; Mutagenesis ; Photoreceptors, Plant/*chemistry/genetics/*metabolism ; Protein Conformation ; Protein Multimerization ; Recombinant Fusion Proteins/chemistry/metabolism ; Tryptophan/chemistry ; *Ultraviolet Rays
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  • 25
    Publication Date: 2012-03-01
    Description: The transition path is the tiny fraction of an equilibrium molecular trajectory when a transition occurs as the free-energy barrier between two states is crossed. It is a single-molecule property that contains all the mechanistic information on how a process occurs. As a step toward observing transition paths in protein folding, we determined the average transition-path time for a fast- and a slow-folding protein from a photon-by-photon analysis of fluorescence trajectories in single-molecule Forster resonance energy transfer experiments. Whereas the folding rate coefficients differ by a factor of 10,000, the transition-path times differ by a factor of less than 5, which shows that a fast- and a slow-folding protein take almost the same time to fold when folding actually happens. A very simple model based on energy landscape theory can explain this result.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878298/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878298/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chung, Hoi Sung -- McHale, Kevin -- Louis, John M -- Eaton, William A -- Z99 DK999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2012 Feb 24;335(6071):981-4. doi: 10.1126/science.1215768.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 20892-0520, USA. chunghoi@niddk.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22363011" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/*chemistry ; Carrier Proteins/*chemistry ; Fluorescence Resonance Energy Transfer ; Kinetics ; Likelihood Functions ; Models, Molecular ; Molecular Sequence Data ; Photons ; Protein Conformation ; *Protein Folding ; Protein Interaction Domains and Motifs ; Protein Structure, Tertiary ; Thermodynamics
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  • 26
    Publication Date: 2012-06-02
    Description: C99 is the transmembrane carboxyl-terminal domain of the amyloid precursor protein that is cleaved by gamma-secretase to release the amyloid-beta polypeptides, which are associated with Alzheimer's disease. Nuclear magnetic resonance and electron paramagnetic resonance spectroscopy show that the extracellular amino terminus of C99 includes a surface-embedded "N-helix" followed by a short "N-loop" connecting to the transmembrane domain (TMD). The TMD is a flexibly curved alpha helix, making it well suited for processive cleavage by gamma-secretase. Titration of C99 reveals a binding site for cholesterol, providing mechanistic insight into how cholesterol promotes amyloidogenesis. Membrane-buried GXXXG motifs (G, Gly; X, any amino acid), which have an established role in oligomerization, were also shown to play a key role in cholesterol binding. The structure and cholesterol binding properties of C99 may aid in the design of Alzheimer's therapeutics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528355/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528355/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barrett, Paul J -- Song, Yuanli -- Van Horn, Wade D -- Hustedt, Eric J -- Schafer, Johanna M -- Hadziselimovic, Arina -- Beel, Andrew J -- Sanders, Charles R -- F31 NS077681/NS/NINDS NIH HHS/ -- P01 GM080513/GM/NIGMS NIH HHS/ -- T32 GM008320/GM/NIGMS NIH HHS/ -- T32 GM08320/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Jun 1;336(6085):1168-71. doi: 10.1126/science.1219988.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Center for Structural Biology and Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, TN 37232 USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22654059" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Amyloid beta-Protein Precursor/*chemistry/genetics/*metabolism ; Binding Sites ; Cholesterol/*metabolism ; Electron Spin Resonance Spectroscopy ; Humans ; Micelles ; Molecular Sequence Data ; Mutation ; Nuclear Magnetic Resonance, Biomolecular ; Peptide Fragments/*chemistry/genetics/*metabolism ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary
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  • 27
    Publication Date: 2012-01-24
    Description: Multidentate, noncovalent interactions between small molecules and biopolymer fragments are central to processes ranging from drug action to selective catalysis. We present a versatile and sensitive spectroscopic probe of functional groups engaged in hydrogen bonding in such contexts. This involves measurement of the frequency changes in specific covalent bonds upon complex formation, information drawn from otherwise transient complexes that have been extracted from solution and conformationally frozen near 10 kelvin in gas-phase clusters. Resonances closely associated with individual oscillators are easily identified through site-specific isotopic labeling, as demonstrated by application of the method to an archetypal system involving a synthetic tripeptide known to bind biaryl substrates through tailored hydrogen bonding to catalyze their asymmetric bromination. With such data, calculations readily converge on the plausible operative structures in otherwise computationally prohibitive, high-dimensionality landscapes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038764/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038764/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garand, Etienne -- Kamrath, Michael Z -- Jordan, Peter A -- Wolk, Arron B -- Leavitt, Christopher M -- McCoy, Anne B -- Miller, Scott J -- Johnson, Mark A -- R01-GM068649/GM/NIGMS NIH HHS/ -- R37 GM068649/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Feb 10;335(6069):694-8. doi: 10.1126/science.1214948. Epub 2012 Jan 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sterling Chemistry Laboratory, Yale University, Post Office Box 208107, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22267579" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Biphenyl Compounds/*chemistry ; Catalysis ; Freezing ; Gases ; Halogenation ; Hydrogen Bonding ; Infrared Rays ; Molecular Conformation ; Molecular Structure ; Oligopeptides/*chemistry ; Physicochemical Processes ; Spectrum Analysis/*methods ; Stereoisomerism
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  • 28
    Publication Date: 2012-05-26
    Description: Acyl acid amido synthetases of the GH3 family act as critical prereceptor modulators of plant hormone action; however, the molecular basis for their hormone selectivity is unclear. Here, we report the crystal structures of benzoate-specific Arabidopsis thaliana AtGH3.12/PBS3 and jasmonic acid-specific AtGH3.11/JAR1. These structures, combined with biochemical analysis, define features for the conjugation of amino acids to diverse acyl acid substrates and highlight the importance of conformational changes in the carboxyl-terminal domain for catalysis. We also identify residues forming the acyl acid binding site across the GH3 family and residues critical for amino acid recognition. Our results demonstrate how a highly adaptable three-dimensional scaffold is used for the evolution of promiscuous activity across an enzyme family for modulation of plant signaling molecules.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Westfall, Corey S -- Zubieta, Chloe -- Herrmann, Jonathan -- Kapp, Ulrike -- Nanao, Max H -- Jez, Joseph M -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Jun 29;336(6089):1708-11. doi: 10.1126/science.1221863. Epub 2012 May 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Washington University, St. Louis, MO 63130, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22628555" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acids/chemistry/metabolism ; Arabidopsis ; Arabidopsis Proteins/*chemistry/metabolism ; Benzoates/chemistry ; Binding Sites ; Crystallography, X-Ray ; Cyclopentanes/chemistry ; Indoleacetic Acids/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nucleotidyltransferases/*chemistry/metabolism ; Oxylipins/chemistry ; Plant Growth Regulators/chemistry/metabolism ; Protein Structure, Tertiary ; Structure-Activity Relationship ; Substrate Specificity
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  • 29
    Publication Date: 2012-11-10
    Description: Millions of molecules of lipopolysaccharide (LPS) must be assembled on the Escherichia coli cell surface each time the cell divides. The biogenesis of LPS requires seven essential lipopolysaccharide transport (Lpt) proteins to move LPS from the inner membrane through the periplasm to the cell surface. However, no intermediate transport states have been observed. We developed methods to observe intermediate LPS molecules bound to Lpt proteins in the process of being transported in vivo. Movement of individual LPS molecules along these binding sites required multiple rounds of adenosine triphosphate (ATP) hydrolysis in vitro, which suggests that ATP is used to push a continuous stream of LPS through a transenvelope bridge in discrete steps against a concentration gradient.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3552488/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3552488/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okuda, Suguru -- Freinkman, Elizaveta -- Kahne, Daniel -- AI081059/AI/NIAID NIH HHS/ -- GM066174/GM/NIGMS NIH HHS/ -- R01 AI081059/AI/NIAID NIH HHS/ -- R01 GM066174/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Nov 30;338(6111):1214-7. doi: 10.1126/science.1228984. Epub 2012 Nov 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23138981" target="_blank"〉PubMed〈/a〉
    Keywords: ATP-Binding Cassette Transporters/chemistry/metabolism ; Adenosine Triphosphate/*metabolism ; Bacterial Proteins/chemistry/metabolism ; Biological Transport ; Carrier Proteins/chemistry/genetics/metabolism ; Cytoplasm/*metabolism ; Escherichia coli/*metabolism ; Escherichia coli Proteins/chemistry/genetics/metabolism ; Hydrolysis ; Lipopolysaccharides/*metabolism ; Membrane Proteins/chemistry/genetics/metabolism ; Mutation ; Periplasm/*metabolism ; Protein Conformation
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  • 30
    Publication Date: 2012-01-10
    Description: DNA recognition by TAL effectors is mediated by tandem repeats, each 33 to 35 residues in length, that specify nucleotides via unique repeat-variable diresidues (RVDs). The crystal structure of PthXo1 bound to its DNA target was determined by high-throughput computational structure prediction and validated by heavy-atom derivatization. Each repeat forms a left-handed, two-helix bundle that presents an RVD-containing loop to the DNA. The repeats self-associate to form a right-handed superhelix wrapped around the DNA major groove. The first RVD residue forms a stabilizing contact with the protein backbone, while the second makes a base-specific contact to the DNA sense strand. Two degenerate amino-terminal repeats also interact with the DNA. Containing several RVDs and noncanonical associations, the structure illustrates the basis of TAL effector-DNA recognition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427646/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427646/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mak, Amanda Nga-Sze -- Bradley, Philip -- Cernadas, Raul A -- Bogdanove, Adam J -- Stoddard, Barry L -- R01 GM049857/GM/NIGMS NIH HHS/ -- R01 GM088277/GM/NIGMS NIH HHS/ -- R01 GM098861/GM/NIGMS NIH HHS/ -- R01GM098861/GM/NIGMS NIH HHS/ -- RL1 0CA833133/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2012 Feb 10;335(6069):716-9. doi: 10.1126/science.1216211. Epub 2012 Jan 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, A3-025 Seattle, WA 98019, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22223736" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/*chemistry/*metabolism ; Binding Sites ; Crystallography, X-Ray ; DNA, Plant/*chemistry/*metabolism ; DNA-Binding Proteins/chemistry/metabolism ; High-Throughput Screening Assays ; Hydrogen Bonding ; Models, Molecular ; Molecular Sequence Data ; Physicochemical Processes ; Protein Binding ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Repetitive Sequences, Amino Acid ; Virulence Factors/*chemistry/*metabolism ; Xanthomonas/*chemistry/pathogenicity
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  • 31
    Publication Date: 2012-11-01
    Description: To ensure their stable inheritance by daughter cells during cell division, bacterial low-copy-number plasmids make simple DNA segregating machines that use an elongating protein filament between sister plasmids. In the ParMRC system of the Escherichia coli R1 plasmid, ParM, an actinlike protein, forms the spindle between ParRC complexes on sister plasmids. By using a combination of structural work and total internal reflection fluorescence microscopy, we show that ParRC bound and could accelerate growth at only one end of polar ParM filaments, mechanistically resembling eukaryotic formins. The architecture of ParM filaments enabled two ParRC-bound filaments to associate in an antiparallel orientation, forming a bipolar spindle. The spindle elongated as a bundle of at least two antiparallel filaments, thereby pushing two plasmid clusters toward the poles.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694215/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694215/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gayathri, P -- Fujii, T -- Moller-Jensen, J -- van den Ent, F -- Namba, K -- Lowe, J -- MC_U105184326/Medical Research Council/United Kingdom -- U.1051.04.014(78932)/Medical Research Council/United Kingdom -- U105184326/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2012 Dec 7;338(6112):1334-7. doi: 10.1126/science.1229091. Epub 2012 Oct 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23112295" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/*chemistry/*metabolism ; Actins/*chemistry/*metabolism ; Adenylyl Imidodiphosphate/chemistry/metabolism ; Cell Division/*genetics ; Cryoelectron Microscopy ; DNA, Bacterial/chemistry/*metabolism ; Escherichia coli/*genetics/physiology ; Escherichia coli Proteins/*chemistry/*metabolism ; Protein Conformation ; R Factors/*genetics
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  • 32
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-12-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2012 Dec 14;338(6113):1408-11. doi: 10.1126/science.338.6113.1408.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23239709" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/chemistry/genetics/*metabolism ; Base Sequence ; Capsicum/microbiology ; Deoxyribonucleases/chemistry/genetics/*metabolism ; Gene Targeting/*methods ; Genetic Engineering/*methods ; Genome ; Humans ; Malus/microbiology ; Protein Conformation ; Trans-Activators/chemistry/genetics/*metabolism ; Virulence Factors/chemistry/genetics/*metabolism ; Xanthomonas/genetics/*metabolism/pathogenicity ; *Zinc Fingers
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  • 33
    Publication Date: 2012-07-28
    Description: Membrane-integral pyrophosphatases (M-PPases) are crucial for the survival of plants, bacteria, and protozoan parasites. They couple pyrophosphate hydrolysis or synthesis to Na(+) or H(+) pumping. The 2.6-angstrom structure of Thermotoga maritima M-PPase in the resting state reveals a previously unknown solution for ion pumping. The hydrolytic center, 20 angstroms above the membrane, is coupled to the gate formed by the conserved Asp(243), Glu(246), and Lys(707) by an unusual "coupling funnel" of six alpha helices. Comparison with our 4.0-angstrom resolution structure of the product complex suggests that helix 12 slides down upon substrate binding to open the gate by a simple binding-change mechanism. Below the gate, four helices form the exit channel. Superimposing helices 3 to 6, 9 to 12, and 13 to 16 suggests that M-PPases arose through gene triplication.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kellosalo, Juho -- Kajander, Tommi -- Kogan, Konstantin -- Pokharel, Kisun -- Goldman, Adrian -- New York, N.Y. -- Science. 2012 Jul 27;337(6093):473-6. doi: 10.1126/science.1222505.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology and Biophysics Program, Institute of Biotechnology, Post Office Box 65, University of Helsinki, FIN-00014, Finland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22837527" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/chemistry/genetics/metabolism ; Biocatalysis ; Calcium/chemistry ; Catalytic Domain ; Cell Membrane/enzymology ; Crystallography, X-Ray ; Diphosphates/*metabolism ; Hydrolysis ; Hydrophobic and Hydrophilic Interactions ; Ion Channel Gating ; Magnesium/chemistry ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Pyrophosphatases/*chemistry/genetics/*metabolism ; Sodium/*metabolism ; Sodium-Potassium-Exchanging ATPase/*chemistry/genetics/metabolism ; Thermotoga maritima/*enzymology
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  • 34
    Publication Date: 2012-03-03
    Description: The sulfonamide antibiotics inhibit dihydropteroate synthase (DHPS), a key enzyme in the folate pathway of bacteria and primitive eukaryotes. However, resistance mutations have severely compromised the usefulness of these drugs. We report structural, computational, and mutagenesis studies on the catalytic and resistance mechanisms of DHPS. By performing the enzyme-catalyzed reaction in crystalline DHPS, we have structurally characterized key intermediates along the reaction pathway. Results support an S(N)1 reaction mechanism via formation of a novel cationic pterin intermediate. We also show that two conserved loops generate a substructure during catalysis that creates a specific binding pocket for p-aminobenzoic acid, one of the two DHPS substrates. This substructure, together with the pterin-binding pocket, explains the roles of the conserved active-site residues and reveals how sulfonamide resistance arises.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3531234/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3531234/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yun, Mi-Kyung -- Wu, Yinan -- Li, Zhenmei -- Zhao, Ying -- Waddell, M Brett -- Ferreira, Antonio M -- Lee, Richard E -- Bashford, Donald -- White, Stephen W -- AI070721/AI/NIAID NIH HHS/ -- CA21765/CA/NCI NIH HHS/ -- P30 CA021765/CA/NCI NIH HHS/ -- R01 AI070721/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2012 Mar 2;335(6072):1110-4. doi: 10.1126/science.1214641.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22383850" target="_blank"〉PubMed〈/a〉
    Keywords: 4-Aminobenzoic Acid/chemistry/metabolism ; Amino Acid Sequence ; Anti-Bacterial Agents/chemistry/metabolism/*pharmacology ; Bacillus anthracis/drug effects/enzymology ; Biocatalysis ; Catalytic Domain ; Crystallization ; Crystallography, X-Ray ; Dihydropteroate Synthase/*chemistry/genetics/*metabolism ; Diphosphates/chemistry/metabolism ; *Drug Resistance, Bacterial ; Magnesium/chemistry ; Models, Chemical ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis ; Parabens/chemistry/metabolism ; Protein Conformation ; Sulfamethoxazole/chemistry/metabolism/*pharmacology ; Sulfathiazoles/chemistry/metabolism/*pharmacology ; Yersinia pestis/drug effects/enzymology
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  • 35
    Publication Date: 2012-08-11
    Description: Cells reuse signaling proteins in multiple pathways, raising the potential for improper cross talk. Scaffold proteins are thought to insulate against such miscommunication by sequestering proteins into distinct physical complexes. We show that the scaffold protein Ste5, which organizes the yeast mating mitogen-activated protein kinase (MAPK) pathway, does not use sequestration to prevent misactivation of the mating response. Instead, Ste5 appears to use a conformation mechanism: Under basal conditions, an intramolecular interaction of the pleckstrin homology (PH) domain with the von Willebrand type A (VWA) domain blocks the ability to coactivate the mating-specific MAPK Fus3. Pheromone-induced membrane binding of Ste5 triggers release of this autoinhibition. Thus, in addition to serving as a conduit guiding kinase communication, Ste5 directly receives input information to decide if and when signal can be transmitted to mating output.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631425/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631425/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zalatan, Jesse G -- Coyle, Scott M -- Rajan, Saravanan -- Sidhu, Sachdev S -- Lim, Wendell A -- MOPS-93725/Canadian Institutes of Health Research/Canada -- P41 RR001614/RR/NCRR NIH HHS/ -- P50 GM081879/GM/NIGMS NIH HHS/ -- PN2 EY016546/EY/NEI NIH HHS/ -- R01 GM055040/GM/NIGMS NIH HHS/ -- R01 GM55040/GM/NIGMS NIH HHS/ -- R01 GM62583/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Sep 7;337(6099):1218-22. doi: 10.1126/science.1220683. Epub 2012 Aug 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22878499" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/antagonists & ; inhibitors/*chemistry/*metabolism ; Enzyme Activation ; MAP Kinase Kinase Kinases/metabolism ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Mitogen-Activated Protein Kinases/*metabolism ; Models, Biological ; Phosphorylation ; Protein Conformation ; Protein Interaction Domains and Motifs ; Protein Kinases/metabolism ; Protein Precursors/metabolism ; Saccharomyces cerevisiae/*metabolism/physiology ; Saccharomyces cerevisiae Proteins/antagonists & inhibitors/*chemistry/*metabolism
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  • 36
    Publication Date: 2012-02-11
    Description: DNMT1, the major maintenance DNA methyltransferase in animals, helps to regulate gene expression, genome imprinting, and X-chromosome inactivation. We report on the crystal structure of a productive covalent mouse DNMT1(731-1602)-DNA complex containing a central hemimethylated CpG site. The methyl group of methylcytosine is positioned within a shallow hydrophobic concave surface, whereas the cytosine on the target strand is looped out and covalently anchored within the catalytic pocket. The DNA is distorted at the hemimethylated CpG step, with side chains from catalytic and recognition loops inserting through both grooves to fill an intercalation-type cavity associated with a dual base flip-out on partner strands. Structural and biochemical data establish how a combination of active and autoinhibitory mechanisms ensures the high fidelity of DNMT1-mediated maintenance DNA methylation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4693633/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4693633/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Jikui -- Teplova, Marianna -- Ishibe-Murakami, Satoko -- Patel, Dinshaw J -- P30 CA008748/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2012 Feb 10;335(6069):709-12. doi: 10.1126/science.1214453.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22323818" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/chemistry/metabolism ; Animals ; Base Pairing ; Catalytic Domain ; Crystallography, X-Ray ; DNA/chemistry/*metabolism ; DNA (Cytosine-5-)-Methyltransferase/*chemistry/genetics/*metabolism ; *DNA Methylation ; Dinucleoside Phosphates/chemistry ; Hydrophobic and Hydrophilic Interactions ; Mice ; Models, Molecular ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Substrate Specificity
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  • 37
    Publication Date: 2012-03-01
    Description: Botulinum neurotoxins (BoNTs) are highly poisonous substances that are also effective medicines. Accidental BoNT poisoning often occurs through ingestion of Clostridium botulinum-contaminated food. Here, we present the crystal structure of a BoNT in complex with a clostridial nontoxic nonhemagglutinin (NTNHA) protein at 2.7 angstroms. Biochemical and functional studies show that NTNHA provides large and multivalent binding interfaces to protect BoNT from gastrointestinal degradation. Moreover, the structure highlights key residues in BoNT that regulate complex assembly in a pH-dependent manner. Collectively, our findings define the molecular mechanisms by which NTNHA shields BoNT in the hostile gastrointestinal environment and releases it upon entry into the circulation. These results will assist in the design of small molecules for inhibiting oral BoNT intoxication and of delivery vehicles for oral administration of biologics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545708/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545708/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gu, Shenyan -- Rumpel, Sophie -- Zhou, Jie -- Strotmeier, Jasmin -- Bigalke, Hans -- Perry, Kay -- Shoemaker, Charles B -- Rummel, Andreas -- Jin, Rongsheng -- R01 AI091823/AI/NIAID NIH HHS/ -- U54 AI057159/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2012 Feb 24;335(6071):977-81. doi: 10.1126/science.1214270.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neuroscience, Aging and Stem Cell Research, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22363010" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/*chemistry/metabolism ; Binding Sites ; Botulinum Toxins, Type A/*chemistry/metabolism ; Crystallography, X-Ray ; Hydrogen-Ion Concentration ; Models, Molecular ; Molecular Sequence Data ; Multiprotein Complexes/chemistry/metabolism ; Mutagenesis ; Protein Binding ; Protein Conformation ; Protein Interaction Domains and Motifs ; Protein Structure, Secondary
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  • 38
    Publication Date: 2012-02-11
    Description: In its physiological state, cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) is a tetramer that contains a regulatory (R) subunit dimer and two catalytic (C) subunits. We describe here the 2.3 angstrom structure of full-length tetrameric RIIbeta(2):C(2) holoenzyme. This structure showing a dimer of dimers provides a mechanistic understanding of allosteric activation by cAMP. The heterodimers are anchored together by an interface created by the beta4-beta5 loop in the RIIbeta subunit, which docks onto the carboxyl-terminal tail of the adjacent C subunit, thereby forcing the C subunit into a fully closed conformation in the absence of nucleotide. Diffusion of magnesium adenosine triphosphate (ATP) into these crystals trapped not ATP, but the reaction products, adenosine diphosphate and the phosphorylated RIIbeta subunit. This complex has implications for the dissociation-reassociation cycling of PKA. The quaternary structure of the RIIbeta tetramer differs appreciably from our model of the RIalpha tetramer, confirming the small-angle x-ray scattering prediction that the structures of each PKA tetramer are different.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985767/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985767/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Ping -- Smith-Nguyen, Eric V -- Keshwani, Malik M -- Deal, Michael S -- Kornev, Alexandr P -- Taylor, Susan S -- GM34921/GM/NIGMS NIH HHS/ -- R01 GM034921/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Feb 10;335(6069):712-6. doi: 10.1126/science.1213979.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093-0654, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22323819" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Allosteric Regulation ; Allosteric Site ; Amino Acid Sequence ; Animals ; Binding Sites ; Crystallization ; Crystallography, X-Ray ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/*chemistry/*metabolism ; Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit/*chemistry/*metabolism ; Holoenzymes/chemistry/metabolism ; Hydrophobic and Hydrophilic Interactions ; Mice ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/chemistry/metabolism ; Protein Binding ; Protein Folding ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Rats
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  • 39
    Publication Date: 2012-06-23
    Description: Transcription factors (TFs) are proteins that regulate the expression of genes by binding sequence-specific sites on the chromosome. It has been proposed that to find these sites fast and accurately, TFs combine one-dimensional (1D) sliding on DNA with 3D diffusion in the cytoplasm. This facilitated diffusion mechanism has been demonstrated in vitro, but it has not been shown experimentally to be exploited in living cells. We have developed a single-molecule assay that allows us to investigate the sliding process in living bacteria. Here we show that the lac repressor slides 45 +/- 10 base pairs on chromosomal DNA and that sliding can be obstructed by other DNA-bound proteins near the operator. Furthermore, the repressor frequently (〉90%) slides over its natural lacO(1) operator several times before binding. This suggests a trade-off between rapid search on nonspecific sequences and fast binding at the specific sequence.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hammar, Petter -- Leroy, Prune -- Mahmutovic, Anel -- Marklund, Erik G -- Berg, Otto G -- Elf, Johan -- New York, N.Y. -- Science. 2012 Jun 22;336(6088):1595-8. doi: 10.1126/science.1221648.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22723426" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Chromosomes, Bacterial/metabolism ; DNA, Bacterial/*metabolism ; Escherichia coli/genetics/*metabolism ; Escherichia coli Proteins/*metabolism ; Facilitated Diffusion ; Kinetics ; *Lac Operon ; Lac Repressors/*metabolism ; *Operator Regions, Genetic ; Protein Binding ; Transcription Factors/metabolism
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  • 40
    Publication Date: 2012-03-10
    Description: Amyloid diseases, including Alzheimer's, Parkinson's, and the prion conditions, are each associated with a particular protein in fibrillar form. These amyloid fibrils were long suspected to be the disease agents, but evidence suggests that smaller, often transient and polymorphic oligomers are the toxic entities. Here, we identify a segment of the amyloid-forming protein alphaB crystallin, which forms an oligomeric complex exhibiting properties of other amyloid oligomers: beta-sheet-rich structure, cytotoxicity, and recognition by an oligomer-specific antibody. The x-ray-derived atomic structure of the oligomer reveals a cylindrical barrel, formed from six antiparallel protein strands, that we term a cylindrin. The cylindrin structure is compatible with a sequence segment from the beta-amyloid protein of Alzheimer's disease. Cylindrins offer models for the hitherto elusive structures of amyloid oligomers.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959867/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959867/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Laganowsky, Arthur -- Liu, Cong -- Sawaya, Michael R -- Whitelegge, Julian P -- Park, Jiyong -- Zhao, Minglei -- Pensalfini, Anna -- Soriaga, Angela B -- Landau, Meytal -- Teng, Poh K -- Cascio, Duilio -- Glabe, Charles -- Eisenberg, David -- 016570/PHS HHS/ -- 1R01-AG029430/AG/NIA NIH HHS/ -- 5T32GM008496/GM/NIGMS NIH HHS/ -- P50 AG016570/AG/NIA NIH HHS/ -- R01 AG029430/AG/NIA NIH HHS/ -- R01 AG033069/AG/NIA NIH HHS/ -- RR-15301/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Mar 9;335(6073):1228-31. doi: 10.1126/science.1213151.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, University of California Los Angeles (UCLA), Howard Hughes Medical Institute (HHMI), Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22403391" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amyloid/*chemistry/immunology ; Amyloid beta-Peptides/chemistry ; Antibodies/immunology ; Crystallography, X-Ray ; Hydrogen Bonding ; Models, Molecular ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Peptide Fragments/*chemistry/immunology ; Protein Conformation ; Protein Structure, Tertiary ; Recombinant Proteins/chemistry ; alpha-Crystallin B Chain/*chemistry/immunology
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  • 41
    Publication Date: 2012-01-28
    Description: Two-pore domain potassium (K(+)) channels (K2P channels) control the negative resting potential of eukaryotic cells and regulate cell excitability by conducting K(+) ions across the plasma membrane. Here, we present the 3.4 angstrom resolution crystal structure of a human K2P channel, K2P1 (TWIK-1). Unlike other K(+) channel structures, K2P1 is dimeric. An extracellular cap domain located above the selectivity filter forms an ion pathway in which K(+) ions flow through side portals. Openings within the transmembrane region expose the pore to the lipid bilayer and are filled with electron density attributable to alkyl chains. An interfacial helix appears structurally poised to affect gating. The structure lays a foundation to further investigate how K2P channels are regulated by diverse stimuli.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Alexandria N -- Long, Stephen B -- New York, N.Y. -- Science. 2012 Jan 27;335(6067):432-6. doi: 10.1126/science.1213274.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22282804" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cell Membrane/chemistry ; Crystallization ; Crystallography, X-Ray ; Humans ; Ion Channel Gating ; Lipid Bilayers/chemistry ; Membrane Potentials ; Models, Molecular ; Molecular Sequence Data ; Potassium/metabolism ; Potassium Channels, Tandem Pore Domain/*chemistry/metabolism ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Recombinant Proteins/chemistry
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  • 42
    Publication Date: 2012-06-02
    Description: Designing protein molecules that will assemble into various kinds of ordered materials represents an important challenge in nanotechnology. We report the crystal structure of a 12-subunit protein cage that self-assembles by design to form a tetrahedral structure roughly 16 nanometers in diameter. The strategy of fusing together oligomeric protein domains can be generalized to produce other kinds of cages or extended materials.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lai, Yen-Ting -- Cascio, Duilio -- Yeates, Todd O -- New York, N.Y. -- Science. 2012 Jun 1;336(6085):1129. doi: 10.1126/science.1219351.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of California Los Angeles Biomedical Engineering Interdepartmental Program, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22654051" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Models, Molecular ; Peroxidases/*chemistry ; Protein Conformation ; *Protein Engineering ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits/chemistry ; Proteins/*chemistry ; Viral Matrix Proteins/*chemistry
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  • 43
    Publication Date: 2012-11-28
    Description: Influenza virus ribonucleoprotein complexes (RNPs) are central to the viral life cycle and in adaptation to new host species. RNPs are composed of the viral genome, viral polymerase, and many copies of the viral nucleoprotein. In vitro cell expression of all RNP protein components with four of the eight influenza virus gene segments enabled structural determination of native influenza virus RNPs by means of cryogenic electron microscopy (cryo-EM). The cryo-EM structure reveals the architecture and organization of the native RNP, defining the attributes of its largely helical structure and how polymerase interacts with nucleoprotein and the viral genome. Observations of branched-RNP structures in negative-stain electron microscopy and their putative identification as replication intermediates suggest a mechanism for viral replication by a second polymerase on the RNP template.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578580/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578580/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moeller, Arne -- Kirchdoerfer, Robert N -- Potter, Clinton S -- Carragher, Bridget -- Wilson, Ian A -- 2P41RR017573-11/RR/NCRR NIH HHS/ -- 9 P41 GM103310-11/GM/NIGMS NIH HHS/ -- AI058113/AI/NIAID NIH HHS/ -- GM095573/GM/NIGMS NIH HHS/ -- P01 AI058113/AI/NIAID NIH HHS/ -- P41 GM103310/GM/NIGMS NIH HHS/ -- P50GM073197/GM/NIGMS NIH HHS/ -- R01 GM095573/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Dec 21;338(6114):1631-4. doi: 10.1126/science.1227270. Epub 2012 Nov 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Resource for Automated Molecular Microscopy, Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23180774" target="_blank"〉PubMed〈/a〉
    Keywords: Cryoelectron Microscopy ; Crystallography, X-Ray ; Genome, Viral ; Image Processing, Computer-Assisted ; Influenza A Virus, H1N1 Subtype/*chemistry/genetics/physiology/*ultrastructure ; Microscopy, Electron ; Models, Molecular ; Nucleic Acid Conformation ; Protein Conformation ; Protein Subunits/chemistry/metabolism ; RNA Replicase/*chemistry/metabolism/ultrastructure ; RNA, Viral/*chemistry/metabolism/ultrastructure ; RNA-Binding Proteins/chemistry/metabolism/ultrastructure ; Ribonucleoproteins/*chemistry/genetics/metabolism/ultrastructure ; Transcription, Genetic ; Viral Core Proteins/chemistry/metabolism/ultrastructure ; Viral Proteins/*chemistry/metabolism/ultrastructure ; *Virus Replication
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  • 44
    Publication Date: 2012-11-20
    Description: The epicardium encapsulates the heart and functions as a source of multipotent progenitor cells and paracrine factors essential for cardiac development and repair. Injury of the adult heart results in reactivation of a developmental gene program in the epicardium, but the transcriptional basis of epicardial gene expression has not been delineated. We established a mouse embryonic heart organ culture and gene expression system that facilitated the identification of epicardial enhancers activated during heart development and injury. Epicardial activation of these enhancers depends on a combinatorial transcriptional code centered on CCAAT/enhancer binding protein (C/EBP) transcription factors. Disruption of C/EBP signaling in the adult epicardium reduced injury-induced neutrophil infiltration and improved cardiac function. These findings reveal a transcriptional basis for epicardial activation and heart injury, providing a platform for enhancing cardiac regeneration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613149/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613149/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Guo N -- Thatcher, Jeffrey E -- McAnally, John -- Kong, Yongli -- Qi, Xiaoxia -- Tan, Wei -- DiMaio, J Michael -- Amatruda, James F -- Gerard, Robert D -- Hill, Joseph A -- Bassel-Duby, Rhonda -- Olson, Eric N -- 1K99HL114738/HL/NHLBI NIH HHS/ -- HL100401-01/HL/NHLBI NIH HHS/ -- K99 HL114738/HL/NHLBI NIH HHS/ -- R01 HL077439/HL/NHLBI NIH HHS/ -- R01 HL093039/HL/NHLBI NIH HHS/ -- R01 HL111665/HL/NHLBI NIH HHS/ -- U01 HL100401/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2012 Dec 21;338(6114):1599-603. doi: 10.1126/science.1229765. Epub 2012 Nov 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23160954" target="_blank"〉PubMed〈/a〉
    Keywords: Aldehyde Oxidoreductases/genetics/metabolism ; Animals ; Binding Sites ; CCAAT-Enhancer-Binding Protein-beta/genetics/metabolism ; CCAAT-Enhancer-Binding Protein-delta/genetics/metabolism ; CCAAT-Enhancer-Binding Proteins/genetics/*metabolism ; Enhancer Elements, Genetic ; Female ; *Gene Expression Regulation ; Gene Expression Regulation, Developmental ; Heart/embryology/*physiopathology ; Male ; Mice ; Mice, Transgenic ; Models, Genetic ; Myocardial Contraction ; Myocardial Infarction/*genetics/metabolism ; Myocardial Reperfusion Injury/*genetics/metabolism ; Neutrophil Infiltration ; Oligonucleotide Array Sequence Analysis ; Organ Culture Techniques ; Pericardium/cytology/*embryology/*metabolism ; Signal Transduction ; Uroplakin III/genetics/metabolism ; Ventricular Remodeling ; WT1 Proteins/genetics/metabolism
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  • 45
    Publication Date: 2012-06-02
    Description: Wnts are lipid-modified morphogens that play critical roles in development principally through engagement of Frizzled receptors. The 3.25 angstrom structure of Xenopus Wnt8 (XWnt8) in complex with mouse Frizzled-8 (Fz8) cysteine-rich domain (CRD) reveals an unusual two-domain Wnt structure, not obviously related to known protein folds, resembling a "hand" with "thumb" and "index" fingers extended to grasp the Fz8-CRD at two distinct binding sites. One site is dominated by a palmitoleic acid lipid group projecting from serine 187 at the tip of Wnt's thumb into a deep groove in the Fz8-CRD. In the second binding site, the conserved tip of Wnt's "index finger" forms hydrophobic amino acid contacts with a depression on the opposite side of the Fz8-CRD. The conservation of amino acids in both interfaces appears to facilitate ligand-receptor cross-reactivity, which has important implications for understanding Wnt's functional pleiotropy and for developing Wnt-based drugs for cancer and regenerative medicine.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577348/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577348/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Janda, Claudia Y -- Waghray, Deepa -- Levin, Aron M -- Thomas, Christoph -- Garcia, K Christopher -- R01 GM097015/GM/NIGMS NIH HHS/ -- R01-GM097015/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Jul 6;337(6090):59-64. doi: 10.1126/science.1222879. Epub 2012 May 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22653731" target="_blank"〉PubMed〈/a〉
    Keywords: Acylation ; Amino Acid Sequence ; Animals ; Binding Sites ; Crystallography, X-Ray ; Cysteine/chemistry ; Fatty Acids, Monounsaturated/chemistry ; Glycosylation ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Mice ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; Protein Folding ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, G-Protein-Coupled/*chemistry/metabolism ; Recombinant Proteins/chemistry/metabolism ; Wnt Proteins/*chemistry/metabolism ; Wnt Signaling Pathway ; Xenopus Proteins/*chemistry/metabolism ; Xenopus laevis
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 46
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-04-28
    Description: Argonaute proteins form the functional core of the RNA-induced silencing complexes that mediate RNA silencing in eukaryotes. The 2.3 angstrom resolution crystal structure of human Argonaute2 (Ago2) reveals a bilobed molecule with a central cleft for binding guide and target RNAs. Nucleotides 2 to 6 of a heterogeneous mixture of guide RNAs are positioned in an A-form conformation for base pairing with target messenger RNAs. Between nucleotides 6 and 7, there is a kink that may function in microRNA target recognition or release of sliced RNA products. Tandem tryptophan-binding pockets in the PIWI domain define a likely interaction surface for recruitment of glycine-tryptophan-182 (GW182) or other tryptophan-rich cofactors. These results will enable structure-based approaches for harnessing the untapped therapeutic potential of RNA silencing in humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521581/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521581/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schirle, Nicole T -- MacRae, Ian J -- R01 GM086701/GM/NIGMS NIH HHS/ -- U54 GM074898/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 May 25;336(6084):1037-40. doi: 10.1126/science.1221551. Epub 2012 Apr 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22539551" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Argonaute Proteins/*chemistry/metabolism ; Base Pairing ; Binding Sites ; Crystallography, X-Ray ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; MicroRNAs/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Protein Conformation ; Protein Structure, Tertiary ; RNA Interference ; RNA, Guide/chemistry/metabolism ; RNA, Messenger/chemistry/metabolism ; Tryptophan/chemistry
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  • 47
    Publication Date: 2012-08-04
    Description: Using single-molecule fluorescence resonance energy transfer, we have defined bacterial RNA polymerase (RNAP) clamp conformation at each step in transcription initiation and elongation. We find that the clamp predominantly is open in free RNAP and early intermediates in transcription initiation but closes upon formation of a catalytically competent transcription initiation complex and remains closed during initial transcription and transcription elongation. We show that four RNAP inhibitors interfere with clamp opening. We propose that clamp opening allows DNA to be loaded into and unwound in the RNAP active-center cleft, that DNA loading and unwinding trigger clamp closure, and that clamp closure accounts for the high stability of initiation complexes and the high stability and processivity of elongation complexes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626110/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626110/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chakraborty, Anirban -- Wang, Dongye -- Ebright, Yon W -- Korlann, You -- Kortkhonjia, Ekaterine -- Kim, Taiho -- Chowdhury, Saikat -- Wigneshweraraj, Sivaramesh -- Irschik, Herbert -- Jansen, Rolf -- Nixon, B Tracy -- Knight, Jennifer -- Weiss, Shimon -- Ebright, Richard H -- AI072766/AI/NIAID NIH HHS/ -- BB/E023703/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- GM037554/GM/NIGMS NIH HHS/ -- GM069709/GM/NIGMS NIH HHS/ -- GM069937/GM/NIGMS NIH HHS/ -- GM41376/GM/NIGMS NIH HHS/ -- R01 AI072766/AI/NIAID NIH HHS/ -- R01 GM041376/GM/NIGMS NIH HHS/ -- R01 GM069709/GM/NIGMS NIH HHS/ -- R37 GM041376/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Aug 3;337(6094):591-5. doi: 10.1126/science.1218716.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Waksman Institute, and Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22859489" target="_blank"〉PubMed〈/a〉
    Keywords: DNA Polymerase III/*chemistry/drug effects ; Fluorescence Resonance Energy Transfer/methods ; *Gene Expression Regulation, Bacterial ; Protein Conformation ; *Transcription, Genetic
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  • 48
    Publication Date: 2012-07-17
    Description: Pharmacological responses of G protein-coupled receptors (GPCRs) can be fine-tuned by allosteric modulators. Structural studies of such effects have been limited due to the medium resolution of GPCR structures. We reengineered the human A(2A) adenosine receptor by replacing its third intracellular loop with apocytochrome b(562)RIL and solved the structure at 1.8 angstrom resolution. The high-resolution structure allowed us to identify 57 ordered water molecules inside the receptor comprising three major clusters. The central cluster harbors a putative sodium ion bound to the highly conserved aspartate residue Asp(2.50). Additionally, two cholesterols stabilize the conformation of helix VI, and one of 23 ordered lipids intercalates inside the ligand-binding pocket. These high-resolution details shed light on the potential role of structured water molecules, sodium ions, and lipids/cholesterol in GPCR stabilization and function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399762/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399762/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Wei -- Chun, Eugene -- Thompson, Aaron A -- Chubukov, Pavel -- Xu, Fei -- Katritch, Vsevolod -- Han, Gye Won -- Roth, Christopher B -- Heitman, Laura H -- IJzerman, Adriaan P -- Cherezov, Vadim -- Stevens, Raymond C -- P50 GM073197/GM/NIGMS NIH HHS/ -- R01 GM089857/GM/NIGMS NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Jul 13;337(6091):232-6. doi: 10.1126/science.1219218.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22798613" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine A2 Receptor Agonists/metabolism ; Adenosine A2 Receptor Antagonists/metabolism ; Allosteric Regulation ; Cholesterol/chemistry ; Crystallography, X-Ray ; Cytochrome b Group/chemistry ; Escherichia coli Proteins/chemistry ; HEK293 Cells ; Humans ; Hydrogen Bonding ; Ligands ; Lipid Bilayers ; Lipids/chemistry ; Models, Molecular ; Protein Conformation ; Protein Engineering ; Protein Structure, Secondary ; Receptor, Adenosine A2A/*chemistry/*metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Sodium/*analysis ; Triazines/metabolism ; Triazoles/metabolism ; Water/chemistry
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  • 49
    Publication Date: 2012-01-24
    Description: Tethering a single lysozyme molecule to a carbon nanotube field-effect transistor produced a stable, high-bandwidth transducer for protein motion. Electronic monitoring during 10-minute periods extended well beyond the limitations of fluorescence techniques to uncover dynamic disorder within a single molecule and establish lysozyme as a processive enzyme. On average, 100 chemical bonds are processively hydrolyzed, at 15-hertz rates, before lysozyme returns to its nonproductive, 330-hertz hinge motion. Statistical analysis differentiated single-step hinge closure from enzyme opening, which requires two steps. Seven independent time scales governing lysozyme's activity were observed. The pH dependence of lysozyme activity arises not from changes to its processive kinetics but rather from increasing time spent in either nonproductive rapid motions or an inactive, closed conformation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914775/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914775/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Choi, Yongki -- Moody, Issa S -- Sims, Patrick C -- Hunt, Steven R -- Corso, Brad L -- Perez, Israel -- Weiss, Gregory A -- Collins, Philip G -- R01 CA133592/CA/NCI NIH HHS/ -- R01 CA133592-01/CA/NCI NIH HHS/ -- T32 CA009054/CA/NCI NIH HHS/ -- T32CA009054/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2012 Jan 20;335(6066):319-24. doi: 10.1126/science.1214824.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Surface and Interface Science, University of California Irvine, Irvine, CA 92697-2375, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22267809" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteriophage T4/enzymology ; Biocatalysis ; Electric Conductivity ; Fluorescence Resonance Energy Transfer ; Hydrogen-Ion Concentration ; Kinetics ; Microscopy, Atomic Force ; Muramidase/*chemistry/*metabolism ; Nanotubes, Carbon ; Peptidoglycan/metabolism ; Protein Conformation ; Pyrenes ; Static Electricity ; Thermodynamics ; Transistors, Electronic
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  • 50
    Publication Date: 2012-04-21
    Description: Studying solvation of a large molecule on an atomic level is challenging because of the transient character and inhomogeneity of hydrogen bonding in liquid water. We studied water clusters of a protonated macrocyclic decapeptide, gramicidin S, which were prepared in the gas phase and then cooled to cryogenic temperatures. The experiment spectroscopically tracked fine structural changes of the clusters upon increasing the number of attached water molecules from 1 to 50 and distinguished vibrational fingerprints of different conformers. The data indicate that only the first two water molecules induce a substantial change of the gramicidin S structure by breaking two intramolecular noncovalent bonds. The peptide structure remains largely intact upon further solvation, reflecting the interplay between the strong intramolecular and weaker intermolecular hydrogen bonds.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nagornova, Natalia S -- Rizzo, Thomas R -- Boyarkin, Oleg V -- New York, N.Y. -- Science. 2012 Apr 20;336(6079):320-3. doi: 10.1126/science.1218709.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire de Chimie Physique Moleculaire, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22517854" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Gramicidin/*chemistry ; Hydrogen Bonding ; Nuclear Magnetic Resonance, Biomolecular ; Physicochemical Processes ; Protein Conformation ; Solubility ; Spectrophotometry, Infrared ; Spectrophotometry, Ultraviolet ; Water/chemistry
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  • 51
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-10-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Service, Robert F -- New York, N.Y. -- Science. 2012 Oct 5;338(6103):28. doi: 10.1126/science.338.6103.28.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23042861" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Products/*chemical synthesis/chemistry ; Carbohydrates/chemistry ; *Chemistry Techniques, Synthetic ; Erythropoietin/*chemical synthesis/chemistry ; Pharmaceutical Preparations/*chemical synthesis ; Protein Conformation
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  • 52
    Publication Date: 2012-02-22
    Description: Toll-like receptor 5 (TLR5) binding to bacterial flagellin activates signaling through the transcription factor NF-kappaB and triggers an innate immune response to the invading pathogen. To elucidate the structural basis and mechanistic implications of TLR5-flagellin recognition, we determined the crystal structure of zebrafish TLR5 (as a variable lymphocyte receptor hybrid protein) in complex with the D1/D2/D3 fragment of Salmonella flagellin, FliC, at 2.47 angstrom resolution. TLR5 interacts primarily with the three helices of the FliC D1 domain using its lateral side. Two TLR5-FliC 1:1 heterodimers assemble into a 2:2 tail-to-tail signaling complex that is stabilized by quaternary contacts of the FliC D1 domain with the convex surface of the opposing TLR5. The proposed signaling mechanism is supported by structure-guided mutagenesis and deletion analyses on CBLB502, a therapeutic protein derived from FliC.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406927/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406927/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yoon, Sung-il -- Kurnasov, Oleg -- Natarajan, Venkatesh -- Hong, Minsun -- Gudkov, Andrei V -- Osterman, Andrei L -- Wilson, Ian A -- AI042266/AI/NIAID NIH HHS/ -- R01 AI042266/AI/NIAID NIH HHS/ -- R01 AI042266-05/AI/NIAID NIH HHS/ -- R01 AI080446/AI/NIAID NIH HHS/ -- R01 AI080446-05/AI/NIAID NIH HHS/ -- RC2 AI087616/AI/NIAID NIH HHS/ -- RC2 AI087616-02/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2012 Feb 17;335(6070):859-64. doi: 10.1126/science.1215584.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22344444" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Crystallography, X-Ray ; Dimerization ; Flagellin/*chemistry/metabolism ; Models, Molecular ; Mutagenesis ; Protein Conformation ; Salmonella enterica ; *Signal Transduction ; Structure-Activity Relationship ; Toll-Like Receptor 5/*chemistry/genetics/metabolism ; Zebrafish ; Zebrafish Proteins/*chemistry/genetics/metabolism
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  • 53
    Publication Date: 2012-03-03
    Description: Enterovirus 71 is a picornavirus associated with fatal neurological illness in infants and young children. Here, we report the crystal structure of enterovirus 71 and show that, unlike in other enteroviruses, the "pocket factor," a small molecule that stabilizes the virus, is partly exposed on the floor of the "canyon." Thus, the structure of antiviral compounds may require a hydrophilic head group designed to interact with residues at the entrance of the pocket.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448362/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448362/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Plevka, Pavel -- Perera, Rushika -- Cardosa, Jane -- Kuhn, Richard J -- Rossmann, Michael G -- AI11219/AI/NIAID NIH HHS/ -- R37 AI011219/AI/NIAID NIH HHS/ -- RR007707/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2012 Jun 8;336(6086):1274. doi: 10.1126/science.1218713. Epub 2012 Mar 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22383808" target="_blank"〉PubMed〈/a〉
    Keywords: Capsid/chemistry/metabolism/ultrastructure ; Capsid Proteins/*chemistry/metabolism ; Crystallography, X-Ray ; Enterovirus A, Human/*chemistry/metabolism/*ultrastructure ; Humans ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Protein Conformation ; Receptors, Virus/metabolism
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  • 54
    Publication Date: 2012-05-19
    Description: Eubacteria inactivate their ribosomes as 100S dimers or 70S monomers upon entry into stationary phase. In Escherichia coli, 100S dimer formation is mediated by ribosome modulation factor (RMF) and hibernation promoting factor (HPF), or alternatively, the YfiA protein inactivates ribosomes as 70S monomers. Here, we present high-resolution crystal structures of the Thermus thermophilus 70S ribosome in complex with each of these stationary-phase factors. The binding site of RMF overlaps with that of the messenger RNA (mRNA) Shine-Dalgarno sequence, which prevents the interaction between the mRNA and the 16S ribosomal RNA. The nearly identical binding sites of HPF and YfiA overlap with those of the mRNA, transfer RNA, and initiation factors, which prevents translation initiation. The binding of RMF and HPF, but not YfiA, to the ribosome induces a conformational change of the 30S head domain that promotes 100S dimer formation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377384/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377384/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Polikanov, Yury S -- Blaha, Gregor M -- Steitz, Thomas A -- GM022778/GM/NIGMS NIH HHS/ -- P01 GM022778/GM/NIGMS NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 May 18;336(6083):915-8. doi: 10.1126/science.1218538.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22605777" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*biosynthesis ; Binding Sites ; Crystallography, X-Ray ; Escherichia coli Proteins/*chemistry/metabolism ; Models, Molecular ; Peptide Chain Initiation, Translational ; Prokaryotic Initiation Factors/metabolism ; Protein Binding ; Protein Conformation ; Protein Structure, Tertiary ; RNA, Bacterial/chemistry/metabolism ; RNA, Messenger/chemistry/metabolism ; RNA, Ribosomal, 16S/chemistry/metabolism ; RNA, Transfer/chemistry/metabolism ; Ribosomal Proteins/*chemistry/metabolism ; Ribosome Subunits, Small, Bacterial/chemistry/metabolism/ultrastructure ; Ribosomes/*chemistry/metabolism/ultrastructure ; Thermus thermophilus/*chemistry
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  • 55
    Publication Date: 2012-10-23
    Description: During transcription initiation, RNA polymerase (RNAP) binds and unwinds promoter DNA to form an RNAP-promoter open complex. We have determined crystal structures at 2.9 and 3.0 A resolution of functional transcription initiation complexes comprising Thermus thermophilus RNA polymerase, sigma(A), and a promoter DNA fragment corresponding to the transcription bubble and downstream double-stranded DNA of the RNAP-promoter open complex. The structures show that sigma recognizes the -10 element and discriminator element through interactions that include the unstacking and insertion into pockets of three DNA bases and that RNAP recognizes the -4/+2 region through interactions that include the unstacking and insertion into a pocket of the +2 base. The structures further show that interactions between sigma and template-strand single-stranded DNA (ssDNA) preorganize template-strand ssDNA to engage the RNAP active center.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3593053/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3593053/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Yu -- Feng, Yu -- Chatterjee, Sujoy -- Tuske, Steve -- Ho, Mary X -- Arnold, Eddy -- Ebright, Richard H -- AI072766/AI/NIAID NIH HHS/ -- GM41376/GM/NIGMS NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 AI072766/AI/NIAID NIH HHS/ -- R01 GM041376/GM/NIGMS NIH HHS/ -- R37 GM041376/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Nov 23;338(6110):1076-80. doi: 10.1126/science.1227786. Epub 2012 Oct 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Waksman Institute, and Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23086998" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; DNA, Single-Stranded/chemistry ; DNA-Directed RNA Polymerases/*chemistry ; *Gene Expression Regulation, Bacterial ; Promoter Regions, Genetic ; Protein Conformation ; Sigma Factor/*chemistry ; Thermus thermophilus/*enzymology/*genetics ; *Transcription Initiation, Genetic
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  • 56
    Publication Date: 2012-11-10
    Description: Fluorescent proteins (FPs) are widely used as optical sensors, whereas other light-absorbing domains have been used for optical control of protein localization or activity. Here, we describe light-dependent dissociation and association in a mutant of the photochromic FP Dronpa, and we used it to control protein activities with light. We created a fluorescent light-inducible protein design in which Dronpa domains are fused to both termini of an enzyme domain. In the dark, the Dronpa domains associate and cage the protein, but light induces Dronpa dissociation and activates the protein. This method enabled optical control over guanine nucleotide exchange factor and protease domains without extensive screening. Our findings extend the applications of FPs from exclusively sensing functions to also encompass optogenetic control.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3702057/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3702057/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Xin X -- Chung, Hokyung K -- Lam, Amy J -- Lin, Michael Z -- R01 NS076860/NS/NINDS NIH HHS/ -- R01NS076860/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2012 Nov 9;338(6108):810-4. doi: 10.1126/science.1226854.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23139335" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Vesicular Transport/chemistry/genetics/metabolism ; Animals ; Cell Membrane/metabolism ; Darkness ; Fluorescence ; HeLa Cells ; Humans ; *Light ; Luminescent Proteins/*chemistry/genetics/metabolism ; Mice ; Models, Molecular ; NIH 3T3 Cells ; Native Polyacrylamide Gel Electrophoresis ; Optogenetics ; Protein Conformation ; Protein Engineering ; Protein Multimerization ; *Protein Structure, Tertiary ; Pseudopodia/metabolism/ultrastructure ; Recombinant Fusion Proteins/*chemistry/genetics/metabolism ; Serine Endopeptidases/chemistry/genetics/metabolism ; Viral Nonstructural Proteins/chemistry/genetics/metabolism
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  • 57
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-06-23
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942086/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942086/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prusiner, Stanley B -- P01 AG002132/AG/NIA NIH HHS/ -- P01 AG010770/AG/NIA NIH HHS/ -- P01 AG021601/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2012 Jun 22;336(6088):1511-3. doi: 10.1126/science.1222951.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Neurodegenerative Diseases and Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA. stanley@ind.ucsf.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22723400" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Fungal Proteins/chemistry/metabolism ; Humans ; Neurodegenerative Diseases/*etiology/*metabolism ; Prion Diseases/*etiology/metabolism ; Prions/*chemistry/metabolism/*pathogenicity ; Protein Conformation
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  • 58
    Publication Date: 2012-11-03
    Description: Ribosomal proteins are synthesized in the cytoplasm, before nuclear import and assembly with ribosomal RNA (rRNA). Little is known about coordination of nucleocytoplasmic transport with ribosome assembly. Here, we identify a transport adaptor, symportin 1 (Syo1), that facilitates synchronized coimport of the two 5S-rRNA binding proteins Rpl5 and Rpl11. In vitro studies revealed that Syo1 concomitantly binds Rpl5-Rpl11 and furthermore recruits the import receptor Kap104. The Syo1-Rpl5-Rpl11 import complex is released from Kap104 by RanGTP and can be directly transferred onto the 5S rRNA. Syo1 can shuttle back to the cytoplasm by interaction with phenylalanine-glycine nucleoporins. X-ray crystallography uncovered how the alpha-solenoid symportin accommodates the Rpl5 amino terminus, normally bound to 5S rRNA, in an extended groove. Symportin-mediated coimport of Rpl5-Rpl11 could ensure coordinated and stoichiometric incorporation of these proteins into pre-60S ribosomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kressler, Dieter -- Bange, Gert -- Ogawa, Yutaka -- Stjepanovic, Goran -- Bradatsch, Bettina -- Pratte, Dagmar -- Amlacher, Stefan -- Strauss, Daniela -- Yoneda, Yoshihiro -- Katahira, Jun -- Sinning, Irmgard -- Hurt, Ed -- New York, N.Y. -- Science. 2012 Nov 2;338(6107):666-71. doi: 10.1126/science.1226960.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biochemie-Zentrum der Universitat Heidelberg, Im Neuenheimer Feld 328, Heidelberg D-69120, Germany. dieter.kressler@unifr.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23118189" target="_blank"〉PubMed〈/a〉
    Keywords: *Active Transport, Cell Nucleus ; Amino Acid Sequence ; Base Sequence ; Cell Nucleus/*metabolism ; Chaetomium/metabolism ; Crystallography, X-Ray ; Fungal Proteins/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; Protein Conformation ; Protein Multimerization ; Protein Structure, Tertiary ; RNA, Fungal/metabolism ; RNA, Ribosomal, 5S/metabolism ; RNA-Binding Proteins/chemistry/*metabolism ; Ribosomal Proteins/chemistry/*metabolism ; Ribosomes/*metabolism ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/*metabolism ; beta Karyopherins/metabolism
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  • 59
    Publication Date: 2012-01-10
    Description: TAL (transcription activator-like) effectors, secreted by phytopathogenic bacteria, recognize host DNA sequences through a central domain of tandem repeats. Each repeat comprises 33 to 35 conserved amino acids and targets a specific base pair by using two hypervariable residues [known as repeat variable diresidues (RVDs)] at positions 12 and 13. Here, we report the crystal structures of an 11.5-repeat TAL effector in both DNA-free and DNA-bound states. Each TAL repeat comprises two helices connected by a short RVD-containing loop. The 11.5 repeats form a right-handed, superhelical structure that tracks along the sense strand of DNA duplex, with RVDs contacting the major groove. The 12th residue stabilizes the RVD loop, whereas the 13th residue makes a base-specific contact. Understanding DNA recognition by TAL effectors may facilitate rational design of DNA-binding proteins with biotechnological applications.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586824/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3586824/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deng, Dong -- Yan, Chuangye -- Pan, Xiaojing -- Mahfouz, Magdy -- Wang, Jiawei -- Zhu, Jian-Kang -- Shi, Yigong -- Yan, Nieng -- R01 GM070795/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Feb 10;335(6069):720-3. doi: 10.1126/science.1215670. Epub 2012 Jan 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Bio-Membrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22223738" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/*chemistry/*metabolism ; Base Sequence ; Crystallography, X-Ray ; DNA/chemistry/*metabolism ; DNA-Binding Proteins/chemistry/metabolism ; Hydrogen Bonding ; Models, Molecular ; Molecular Sequence Data ; Physicochemical Processes ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Repetitive Sequences, Amino Acid ; Virulence Factors/*chemistry/*metabolism ; Xanthomonas/chemistry/pathogenicity
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  • 60
    Publication Date: 2012-12-01
    Description: The Trypanosoma brucei cysteine protease cathepsin B (TbCatB), which is involved in host protein degradation, is a promising target to develop new treatments against sleeping sickness, a fatal disease caused by this protozoan parasite. The structure of the mature, active form of TbCatB has so far not provided sufficient information for the design of a safe and specific drug against T. brucei. By combining two recent innovations, in vivo crystallization and serial femtosecond crystallography, we obtained the room-temperature 2.1 angstrom resolution structure of the fully glycosylated precursor complex of TbCatB. The structure reveals the mechanism of native TbCatB inhibition and demonstrates that new biomolecular information can be obtained by the "diffraction-before-destruction" approach of x-ray free-electron lasers from hundreds of thousands of individual microcrystals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3786669/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3786669/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Redecke, Lars -- Nass, Karol -- DePonte, Daniel P -- White, Thomas A -- Rehders, Dirk -- Barty, Anton -- Stellato, Francesco -- Liang, Mengning -- Barends, Thomas R M -- Boutet, Sebastien -- Williams, Garth J -- Messerschmidt, Marc -- Seibert, M Marvin -- Aquila, Andrew -- Arnlund, David -- Bajt, Sasa -- Barth, Torsten -- Bogan, Michael J -- Caleman, Carl -- Chao, Tzu-Chiao -- Doak, R Bruce -- Fleckenstein, Holger -- Frank, Matthias -- Fromme, Raimund -- Galli, Lorenzo -- Grotjohann, Ingo -- Hunter, Mark S -- Johansson, Linda C -- Kassemeyer, Stephan -- Katona, Gergely -- Kirian, Richard A -- Koopmann, Rudolf -- Kupitz, Chris -- Lomb, Lukas -- Martin, Andrew V -- Mogk, Stefan -- Neutze, Richard -- Shoeman, Robert L -- Steinbrener, Jan -- Timneanu, Nicusor -- Wang, Dingjie -- Weierstall, Uwe -- Zatsepin, Nadia A -- Spence, John C H -- Fromme, Petra -- Schlichting, Ilme -- Duszenko, Michael -- Betzel, Christian -- Chapman, Henry N -- 1R01GM095583/GM/NIGMS NIH HHS/ -- R01 GM095583/GM/NIGMS NIH HHS/ -- U54 GM094599/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jan 11;339(6116):227-30. doi: 10.1126/science.1229663. Epub 2012 Nov 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Joint Laboratory for Structural Biology of Infection and Inflammation, Institute of Biochemistry and Molecular Biology, University of Hamburg, and Institute of Biochemistry, University of Lubeck, at Deutsches Elektronen-Synchrotron, Notkestrasse 85, 22607 Hamburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23196907" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Catalytic Domain ; Cathepsin B/antagonists & inhibitors/*chemistry ; Crystallization ; Crystallography, X-Ray ; Enzyme Precursors/chemistry ; Glycosylation ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protozoan Proteins/antagonists & inhibitors/*chemistry ; Sf9 Cells ; Spodoptera ; Trypanosoma brucei brucei/*enzymology ; X-Rays
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  • 61
    Publication Date: 1994-05-13
    Description: In Drosophila, the misexpression or altered activity of genes from the bithorax complex results in homeotic transformations. One of these genes, abd-A, normally specifies the identity of the second through fourth abdominal segments (A2 to A4). In the dominant Hyperabdominal mutations (Hab), portions of the third thoracic segment (T3) are transformed toward A2 as the result of ectopic abd-A expression. Sequence analysis and deoxyribonuclease I footprinting demonstrate that the misexpression of abd-A in two independent Hab mutations results from the same single base change in a binding site for the gap gene Kruppel protein. These results establish that the spatial limits of the homeotic genes are directly regulated by gap gene products.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shimell, M J -- Simon, J -- Bender, W -- O'Connor, M B -- New York, N.Y. -- Science. 1994 May 13;264(5161):968-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Biochemistry, University of California, Irvine 92717.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7909957" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; DNA-Binding Proteins/genetics/metabolism ; *Drosophila Proteins ; Drosophila melanogaster/embryology/*genetics ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation ; *Genes, Homeobox ; Genes, Insect ; Kruppel-Like Transcription Factors ; Molecular Sequence Data ; *Nuclear Proteins ; *Point Mutation ; Proteins/*genetics ; Regulatory Sequences, Nucleic Acid ; *Repressor Proteins ; Transcription Factors/genetics/metabolism
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  • 62
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1994-11-25
    Description: The splicing of group II introns occurs in two steps involving substrates with different chemical configurations. The question of whether these two steps are catalyzed by a single or two separate active sites is a matter of debate. Here, certain bases and phosphate oxygen atoms at conserved positions in domain V of a group II self-splicing intron are shown to be required for catalysis of both splicing steps. These results show that the active sites catalyzing the two steps must, at least, share common components, ruling out the existence of two completely distinct active sites in group II introns.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chanfreau, G -- Jacquier, A -- New York, N.Y. -- Science. 1994 Nov 25;266(5189):1383-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Unite de Genetique Moleculaire des Levures, URA 1149 du CNRS, Departement de Biologie Moleculaire, Institut Pasteur, Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7973729" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; Catalysis ; Electron Transport Complex IV/genetics ; Electrophoresis, Polyacrylamide Gel ; Exons ; *Introns ; Molecular Sequence Data ; Nucleic Acid Conformation ; *RNA Splicing ; RNA, Fungal/chemistry/*genetics ; Saccharomyces cerevisiae/enzymology/genetics ; Thionucleotides/genetics
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  • 63
    Publication Date: 1994-10-14
    Description: The rate at which the TATA-binding protein (TBP) interacts with the TATA element and promotes transcription by RNA polymerase II was determined in yeast cells. A TBP derivative with altered TATA-element specificity was rapidly induced, and transcription from promoters with appropriately mutated TATA elements was measured. Without a functional activator protein, basal transcription was observed only after a lag of several hours. In contrast, GCN4-activated transcription occurred rapidly upon induction of the TBP derivative. These results suggest that accessibility of TBP to the chromatin template in vivo is rate limiting and that activation domains increase recruitment of TBP to the promoter.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Klein, C -- Struhl, K -- GM30186/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1994 Oct 14;266(5183):280-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7939664" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; Chromatin/metabolism ; Copper/pharmacology ; DNA-Binding Proteins/*metabolism ; Fungal Proteins/metabolism/pharmacology ; Hydro-Lyases/genetics ; Molecular Sequence Data ; Protein Kinases/metabolism/pharmacology ; *Saccharomyces cerevisiae Proteins ; *TATA Box ; TATA-Box Binding Protein ; Templates, Genetic ; Transcription Factors/*metabolism/pharmacology ; *Transcriptional Activation ; Yeasts/genetics
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  • 64
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1994-12-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pelletier, H -- New York, N.Y. -- Science. 1994 Dec 23;266(5193):2025-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7801132" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Biological Evolution ; Catalysis ; DNA Polymerase I/*chemistry/metabolism ; Protein Structure, Secondary
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  • 65
    Publication Date: 1994-06-24
    Description: Two ternary complexes of rat DNA polymerase beta (pol beta), a DNA template-primer, and dideoxycytidine triphosphate (ddCTP) have been determined at 2.9 A and 3.6 A resolution, respectively. ddCTP is the triphosphate of dideoxycytidine (ddC), a nucleoside analog that targets the reverse transcriptase of human immunodeficiency virus (HIV) and is at present used to treat AIDS. Although crystals of the two complexes belong to different space groups, the structures are similar, suggesting that the polymerase-DNA-ddCTP interactions are not affected by crystal packing forces. In the pol beta active site, the attacking 3'-OH of the elongating primer, the ddCTP phosphates, and two Mg2+ ions are all clustered around Asp190, Asp192, and Asp256. Two of these residues, Asp190 and Asp256, are present in the amino acid sequences of all polymerases so far studied and are also spatially similar in the four polymerases--the Klenow fragment of Escherichia coli DNA polymerase I, HIV-1 reverse transcriptase, T7 RNA polymerase, and rat DNA pol beta--whose crystal structures are now known. A two-metal ion mechanism is described for the nucleotidyl transfer reaction and may apply to all polymerases. In the ternary complex structures analyzed, pol beta binds to the DNA template-primer in a different manner from that recently proposed for other polymerase-DNA models.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pelletier, H -- Sawaya, M R -- Kumar, A -- Wilson, S H -- Kraut, J -- CA17374/CA/NCI NIH HHS/ -- ES06839/ES/NIEHS NIH HHS/ -- GM10928/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1994 Jun 24;264(5167):1891-903.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of California, San Diego 92093-0317.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7516580" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Crystallization ; Crystallography, X-Ray ; DNA/chemistry/metabolism ; DNA Polymerase I/*chemistry/metabolism ; DNA Primers/*chemistry/metabolism ; DNA-Directed RNA Polymerases/chemistry/metabolism ; Deoxycytosine Nucleotides/*chemistry/metabolism ; Dideoxynucleotides ; HIV Reverse Transcriptase ; Humans ; Hydrogen Bonding ; Models, Molecular ; Molecular Sequence Data ; RNA-Directed DNA Polymerase/chemistry/metabolism ; Rats ; Recombinant Proteins ; Templates, Genetic ; Thymine Nucleotides/chemistry/metabolism ; Viral Proteins ; Zidovudine/analogs & derivatives/chemistry/metabolism
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  • 66
    Publication Date: 1994-04-01
    Description: The crystal structure of a ternary protein complex has been determined at 2.4 angstrom resolution. The complex is composed of three electron transfer proteins from Paracoccus denitrificans, the quinoprotein methylamine dehydrogenase, the blue copper protein amicyanin, and the cytochrome c551i. The central region of the c551i is folded similarly to several small bacterial c-type cytochromes; there is a 45-residue extension at the amino terminus and a 25-residue extension at the carboxyl terminus. The methylamine dehydrogenase-amicyanin interface is largely hydrophobic, whereas the amicyanin-cytochrome interface is more polar, with several charged groups present on each surface. Analysis of the simplest electron transfer pathways between the redox partners points out the importance of other factors such as energetics in determining the electron transfer rates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, L -- Durley, R C -- Mathews, F S -- Davidson, V L -- GM41574/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1994 Apr 1;264(5155):86-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8140419" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/metabolism ; Computer Graphics ; Cytochrome c Group/*chemistry/metabolism ; Electron Transport ; Hydrogen Bonding ; *Indolequinones ; Models, Molecular ; Oxidation-Reduction ; Oxidoreductases Acting on CH-NH Group Donors/*chemistry/metabolism ; Paracoccus denitrificans/*chemistry/enzymology ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Quinones/chemistry/metabolism ; Software ; Tryptophan/analogs & derivatives/chemistry/metabolism
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  • 67
    Publication Date: 1994-02-04
    Description: The three-dimensional structure of a catalytic antibody (1F7) with chorismate mutase activity has been determined to 3.0 A resolution as a complex with a transition state analog. The structural data suggest that the antibody stabilizes the same conformationally restricted pericyclic transition state as occurs in the uncatalyzed reaction. Overall shape and charge complementarity between the combining site and the transition state analog dictate preferential binding of the correct substrate enantiomer in a conformation appropriate for reaction. Comparison with the structure of a chorismate mutase enzyme indicates an overall similarity between the catalytic mechanism employed by the two proteins. Differences in the number of specific interactions available for restricting the rotational degrees of freedom in the transition state, and the lack of multiple electrostatic interactions that might stabilize charge separation in this highly polarized metastable species, are likely to account for the observed 10(4) times lower activity of the antibody relative to that of the natural enzymes that catalyze this reaction. The structure of the 1F7 Fab'-hapten complex provides confirmation that the properties of an antibody catalyst faithfully reflect the design of the transition state analog.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haynes, M R -- Stura, E A -- Hilvert, D -- Wilson, I A -- AI-23498/AI/NIAID NIH HHS/ -- GM-38273/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1994 Feb 4;263(5147):646-52.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8303271" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Catalytic/*chemistry/metabolism ; Bacillus subtilis/enzymology ; Binding Sites ; Binding Sites, Antibody ; Catalysis ; Chorismate Mutase/*chemistry/metabolism ; Chorismic Acid/metabolism ; Crystallization ; Haptens ; Hydrogen Bonding ; Immunoglobulin Fab Fragments/metabolism ; Models, Molecular ; Thermodynamics
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  • 68
    Publication Date: 1994-06-24
    Description: A 175-kilodalton erythrocyte binding protein, EBA-175, of the parasite Plasmodium falciparum mediates the invasion of erythrocytes. The erythrocyte receptor for EBA-175 is dependent on sialic acid. The domain of EBA-175 that binds erythrocytes was identified as region II with the use of truncated portions of EBA-175 expressed on COS cells. Region II, which contains a cysteine-rich motif, and native EBA-175 bind specifically to glycophorin A, but not to glycophorin B, on the erythrocyte membrane. Erythrocyte recognition of EBA-175 requires both sialic acid and the peptide backbone of glycophorin A. The identification of both the receptor and ligand domains may suggest rational designs for receptor blockade and vaccines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sim, B K -- Chitnis, C E -- Wasniowska, K -- Hadley, T J -- Miller, L H -- New York, N.Y. -- Science. 1994 Jun 24;264(5167):1941-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Malaria Research, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8009226" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antigens, Protozoan ; Base Sequence ; Binding Sites ; Carrier Proteins/genetics/*metabolism ; Cell Line ; Erythrocytes/metabolism/*parasitology ; Glycopeptides/chemistry/metabolism ; Glycophorin/chemistry/*metabolism ; Molecular Sequence Data ; Plasmodium falciparum/*metabolism ; Protozoan Proteins/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Sialic Acids/*metabolism
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  • 69
    Publication Date: 1994-10-21
    Description: The structure of the heterodimeric flavocytochrome c sulfide dehydrogenase from Chromatium vinosum was determined at a resolution of 2.53 angstroms. It contains a glutathione reductase-like flavin-binding subunit and a diheme cytochrome subunit. The diheme cytochrome folds as two domains, each resembling mitochondrial cytochrome c, and has an unusual interpropionic acid linkage joining the two heme groups in the interior of the subunit. The active site of the flavoprotein subunit contains a catalytically important disulfide bridge located above the pyrimidine portion of the flavin ring. A tryptophan, threonine, or tyrosine side chain may provide a partial conduit for electron transfer to one of the heme groups located 10 angstroms from the flavin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Z W -- Koh, M -- Van Driessche, G -- Van Beeumen, J J -- Bartsch, R G -- Meyer, T E -- Cusanovich, M A -- Mathews, F S -- GM-20530/GM/NIGMS NIH HHS/ -- GM-21277/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1994 Oct 21;266(5184):430-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7939681" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Chromatium/*enzymology ; Computer Graphics ; Crystallography, X-Ray ; Cytochrome c Group/*chemistry ; Electron Transport ; Flavin-Adenine Dinucleotide/metabolism ; Hydrogen Bonding ; Models, Molecular ; Oxidoreductases/*chemistry ; Protein Conformation ; Protein Structure, Secondary
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  • 70
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1994-03-11
    Description: Ion transporters can be thought of as ion channels that open and close only at one end at a time. As in real channels, ions may cross through an electrical field as they diffuse into and bind within the transporter pore, thereby generating electrical current. Extracellular sodium binding by the sodium potassium (Na,K) pump is associated with ultrafast charge movements in giant cardiac membrane patches. The charge movements are complete within 4 microseconds. They occur only when binding sites are open to the extracellular side, and they are abolished by ouabain and by the removal of extracellular sodium. Fast extracellular ion binding may be the exclusive source of Na,K pump electrogenicity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hilgemann, D W -- New York, N.Y. -- Science. 1994 Mar 11;263(5152):1429-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8128223" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Binding Sites ; Guinea Pigs ; Membrane Potentials ; Models, Biological ; Myocardium/cytology/*metabolism ; Sodium/*metabolism ; Sodium Channels/*metabolism ; Sodium-Potassium-Exchanging ATPase/*metabolism
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  • 71
    Publication Date: 1994-06-03
    Description: Multi-wavelength anomalous diffraction (MAD) has been used to determine the structure of the regulatory enzyme of de novo synthesis of purine nucleotides, glutamine 5-phosphoribosyl-1-pyrophosphate (PRPP) amidotransferase, from Bacillus subtilis. This allosteric enzyme, a 200-kilodalton tetramer, is subject to end product regulation by purine nucleotides. The metalloenzyme from B. subtilis is a paradigm for the higher eukaryotic enzymes, which have been refractory to isolation in stable form. The two folding domains of the polypeptide are correlated with functional domains for glutamine binding and for transfer of ammonia to the substrate PRPP. Eight molecules of the feedback inhibitor adenosine monophosphate (AMP) are bound to the tetrameric enzyme in two types of binding sites: the PRPP catalytic site of each subunit and an unusual regulatory site that is immediately adjacent to each active site but is between subunits. An oxygen-sensitive [4Fe-4S] cluster in each subunit is proposed to regulate protein turnover in vivo and is distant from the catalytic site. Oxygen sensitivity of the cluster is diminished by AMP, which blocks a channel through the protein to the cluster. The structure is representative of both glutamine amidotransferases and phosphoribosyltransferases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, J L -- Zaluzec, E J -- Wery, J P -- Niu, L -- Switzer, R L -- Zalkin, H -- Satow, Y -- DK-42303/DK/NIDDK NIH HHS/ -- GM-24658/GM/NIGMS NIH HHS/ -- R37 DK042303/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1994 Jun 3;264(5164):1427-33.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Purdue University, West Lafayette, IN 47907.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8197456" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Monophosphate/metabolism ; Allosteric Regulation ; Amidophosphoribosyltransferase/*chemistry/metabolism ; Amino Acid Sequence ; Animals ; Bacillus subtilis/*enzymology ; Binding Sites ; Computer Graphics ; Crystallography, X-Ray ; Humans ; Models, Molecular ; Molecular Sequence Data ; Oxygen/pharmacology ; Protein Folding ; Protein Structure, Secondary ; Saccharomyces cerevisiae
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  • 72
    Publication Date: 1994-06-24
    Description: The structure of the leech protein decorsin, a potent 39-residue antagonist of glycoprotein IIb-IIIa and inhibitor of platelet aggregation, was determined by nuclear magnetic resonance. In contrast to other disintegrins, the Arg-Gly-Asp (RGD)-containing region of decorsin is well defined. The three-dimensional structure of decorsin is similar to that of hirudin, an anticoagulant leech protein that potently inhibits thrombin. Amino acid sequence comparisons suggest that ornatin, another glycoprotein IIb-IIIa antagonist, and antistasin, a potent Factor Xa inhibitor and anticoagulant found in leeches, share the same structural motif. Although decorsin, hirudin, and antistasin all affect the blood clotting process and appear similar in structure, their mechanisms of action and epitopes important for binding to their respective targets are distinct.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krezel, A M -- Wagner, G -- Seymour-Ulmer, J -- Lazarus, R A -- New York, N.Y. -- Science. 1994 Jun 24;264(5167):1944-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8009227" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Hirudins/chemistry ; Invertebrate Hormones/chemistry ; *Leeches ; Magnetic Resonance Spectroscopy ; Molecular Sequence Data ; Oligopeptides/chemistry ; Platelet Membrane Glycoproteins/*antagonists & inhibitors ; Protein Conformation ; Protein Structure, Secondary ; Proteins/*chemistry
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  • 73
    Publication Date: 1994-10-07
    Description: Macrophage-stimulating protein (MSP) is a member of the hepatocyte growth factor-scatter factor (HGF-SF) family. Labeled MSP bound to Madin-Darby canine kidney (MDCK) cells transfected with complementary DNA encoding Ron, a cell membrane protein tyrosine kinase. Cross-linking of 125I-labeled MSP to transfected cells (MDCK-RE7 cells) and immunoprecipitation by antibodies to Ron revealed a 220-kilodalton complex, a size consistent with that of MSP (80 kilodaltons) cross-linked to the beta chain of Ron (150 kilodaltons). The binding of 125I-labeled MSP to MDCK-RE7 cells was inhibited by unlabeled MSP, but not by HGF-SF. MSP caused phosphorylation of the beta chain of Ron and induced migration of MDCK-RE7 cells. These results establish the ron gene product as a specific cell-surface receptor for MSP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, M H -- Ronsin, C -- Gesnel, M C -- Coupey, L -- Skeel, A -- Leonard, E J -- Breathnach, R -- New York, N.Y. -- Science. 1994 Oct 7;266(5182):117-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunopathology Section, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7939629" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Binding, Competitive ; Cell Line ; Cell Movement/drug effects ; Cross-Linking Reagents ; Dogs ; Growth Substances/*metabolism/pharmacology ; Hepatocyte Growth Factor/metabolism ; Humans ; Phosphorylation ; Plasminogen/metabolism ; *Proto-Oncogene Proteins ; Receptor Protein-Tyrosine Kinases/genetics/*metabolism ; Receptors, Cell Surface/genetics/*metabolism ; Transfection
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  • 74
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1994-04-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, F E -- Pan, K M -- Huang, Z -- Baldwin, M -- Fletterick, R J -- Prusiner, S B -- New York, N.Y. -- Science. 1994 Apr 22;264(5158):530-1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of California, San Francisco 94143-0518.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7909169" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Mice ; Mice, Transgenic ; Models, Biological ; Mutation ; PrPSc Proteins ; Prion Diseases/*metabolism/transmission ; Prions/*biosynthesis/chemistry/genetics/metabolism ; Protein Conformation ; Protein Structure, Secondary
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  • 75
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1994-04-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weissmann, C -- New York, N.Y. -- Science. 1994 Apr 22;264(5158):528-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Molecularbiologie I, Universitat Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7909168" target="_blank"〉PubMed〈/a〉
    Keywords: Aspartic Acid/analogs & derivatives/metabolism ; Fungal Proteins/chemistry/*genetics ; Genes, Fungal ; Glutathione Peroxidase ; Mutation ; PrPSc Proteins ; Prions/chemistry/genetics ; Protein Conformation ; Saccharomyces cerevisiae/*genetics/metabolism ; *Saccharomyces cerevisiae Proteins
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  • 76
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1994-03-11
    Description: Protein tyrosine phosphatases (PTPs) constitute a family of receptor-like and cytoplasmic signal transducing enzymes that catalyze the dephosphorylation of phosphotyrosine residues and are characterized by homologous catalytic domains. The crystal structure of a representative member of this family, the 37-kilodalton form (residues 1 to 321) of PTP1B, has been determined at 2.8 A resolution. The enzyme consists of a single domain with the catalytic site located at the base of a shallow cleft. The phosphate recognition site is created from a loop that is located at the amino-terminus of an alpha helix. This site is formed from an 11-residue sequence motif that is diagnostic of PTPs and the dual specificity phosphatases, and that contains the catalytically essential cysteine and arginine residues. The position of the invariant cysteine residue within the phosphate binding site is consistent with its role as a nucleophile in the catalytic reaction. The structure of PTP1B should serve as a model for other members of the PTP family and as a framework for understanding the mechanism of tyrosine dephosphorylation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barford, D -- Flint, A J -- Tonks, N K -- CA53840/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1994 Mar 11;263(5152):1397-404.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉W.M. Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, NY 11724.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8128219" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Computer Graphics ; Crystallography, X-Ray ; Humans ; Models, Molecular ; Molecular Sequence Data ; Phosphates/metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Tyrosine Phosphatases/*chemistry/isolation & purification/metabolism ; Substrate Specificity ; Tungsten Compounds/metabolism
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  • 77
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1994-05-20
    Description: The biological role of RNA is delimited by its possible reactions, which can be explored by selection. A comparison of selected RNAs that bind one ligand with those that bind two related ligands suggests that a single nucleotide substitution can expand binding specificity. An RNA site with dual (joint) specificity has adenine and cytosine bases whose pKa's appear shifted upward, thereby mimicking an efficient general acid-base catalyst. The joint site also contains two conserved, looped arginine-coding triplets implicated in arginine site formation. Two selected joint RNAs are identical in some regions and distinct in others. The distinct regions, like some peptides, seem to function similarly without being similar in primary structure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Connell, G J -- Yarus, M -- New York, N.Y. -- Science. 1994 May 20;264(5162):1137-41.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder 80309-0347.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7513905" target="_blank"〉PubMed〈/a〉
    Keywords: Arginine/*metabolism ; Base Sequence ; Binding Sites ; Chromatography, Affinity ; Consensus Sequence ; Guanosine/*metabolism ; Hydrogen-Ion Concentration ; Molecular Sequence Data ; Nucleic Acid Conformation ; RNA/chemistry/*metabolism ; RNA, Catalytic/chemistry/metabolism
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  • 78
    Publication Date: 1994-10-14
    Description: An engineered variant of subtilisin BPN', termed subtiligase, which efficiently ligates esterified peptides in aqueous solution, was used for the complete synthesis of ribonuclease (RNase) A that contains unnatural catalytic residues. Fully active RNase A (124 residues long) was produced in milligram quantities by stepwise ligation of six esterified peptide fragments (each 12 to 30 residues long) at yields averaging 70 percent per ligation. Variants of RNase A were produced in which the catalytic histidines at positions 12 and 119 were substituted with the unnatural amino acid 4-fluorohistidine, which has a pKa of 3.5 compared to 6.8 for histidine. Large changes in the profile of the pH as it affects rate occurred for the single and double mutants with surprisingly little change in the kcat for either the RNA cleavage or hydrolysis steps. The data indicate that these imidazoles function as general acids and bases, but that the proton transfer steps are not rate-limiting when the imidazoles are present in their correct protonation states. These studies indicate the potential of subtiligase for the blockwise synthesis of large proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jackson, D Y -- Burnier, J -- Quan, C -- Stanley, M -- Tom, J -- Wells, J A -- New York, N.Y. -- Science. 1994 Oct 14;266(5183):243-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Protein Engineering, Genentech, Inc., South San Francisco, CA 94080.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7939659" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Esterification ; Histidine/analogs & derivatives/analysis ; Hydrogen-Ion Concentration ; Molecular Sequence Data ; Mutation ; Nucleotides, Cyclic/metabolism ; Protein Engineering/*methods ; Ribonuclease, Pancreatic/*chemical synthesis/chemistry/isolation & purification ; Subtilisins/chemistry/genetics/*metabolism ; Uridine Monophosphate/metabolism
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  • 79
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1994-10-14
    Description: The trimeric protein hemagglutinin (HA) of the influenza viral envelope is essential for cell entry. To investigate the interaction of HA with membranes, two 40-residue, cysteine-substituted peptides comprising the loop region and the first part of the coiled-coil stem were synthesized and modified with a nitroxide spin label. Electron paramagnetic resonance analysis revealed that the peptide inserts reversibly into phospholipid vesicles under endosomal pH conditions. This result suggests that some or all of the long coiled-coil trimer of HA may insert into membranes, which could bring the viral and cell membranes closer together and facilitate fusion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Y G -- King, D S -- Shin, Y K -- New York, N.Y. -- Science. 1994 Oct 14;266(5183):274-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of California, Berkeley.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7939662" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Electron Spin Resonance Spectroscopy ; Endocytosis ; Hemagglutinin Glycoproteins, Influenza Virus ; Hemagglutinins, Viral/chemistry/*metabolism ; Hydrogen-Ion Concentration ; Lipid Bilayers/*metabolism ; *Membrane Fusion ; Molecular Sequence Data ; Orthomyxoviridae/physiology ; Protein Conformation ; Protein Structure, Secondary ; Temperature ; Viral Envelope Proteins/chemistry/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 80
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1994-09-23
    Description: The functional consequences of single proton transfers occurring in the pore of a cyclic nucleotide-gated channel were observed with patch recording techniques. These results led to three conclusions about the chemical nature of ion binding sites in the conduction pathway: The channel contains two identical titratable sites, even though there are more than two (probably four) identical subunits; the sites are formed by glutamate residues that have a pKa (where K(a) is the acid constant) of 7.6; and protonation of one site does not perturb the pKa of the other. These properties point to an unusual arrangement of carboxyl side-chain residues in the pore of a cation channel.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Root, M J -- MacKinnon, R -- 5 T32 GM083113/GM/NIGMS NIH HHS/ -- GM47400/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1994 Sep 23;265(5180):1852-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7522344" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Calcium Channels/metabolism ; Catfishes ; Electric Conductivity ; Hydrogen-Ion Concentration ; Ion Channel Gating ; Ion Channels/chemistry/genetics/*metabolism ; Kinetics ; Molecular Sequence Data ; Mutation ; *Protons ; Sodium/metabolism ; Xenopus
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  • 81
    Publication Date: 1994-04-29
    Description: Tumor necrosis factor (TNF) and lymphotoxin-alpha (LT-alpha) are members of a family of secreted and cell surface cytokines that participate in the regulation of immune and inflammatory responses. The cell surface form of LT-alpha is assembled during biosynthesis as a heteromeric complex with lymphotoxin-beta (LT-beta), a type II transmembrane protein that is another member of the TNF ligand family. Secreted LT-alpha is a homotrimer that binds to distinct TNF receptors of 60 and 80 kilodaltons; however, these receptors do not recognize the major cell surface LT-alpha-LT-beta complex. A receptor specific for human LT-beta was identified, which suggests that cell surface LT may have functions that are distinct from those of secreted LT-alpha.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crowe, P D -- VanArsdale, T L -- Walter, B N -- Ware, C F -- Hession, C -- Ehrenfels, B -- Browning, J L -- Din, W S -- Goodwin, R G -- Smith, C A -- New York, N.Y. -- Science. 1994 Apr 29;264(5159):707-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biomedical Sciences, University of California, Riverside 92521.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8171323" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Cysteine/chemistry ; Humans ; Hybridomas ; Ligands ; Lymphotoxin beta Receptor ; Lymphotoxin-alpha/*metabolism ; Molecular Sequence Data ; Receptors, Tumor Necrosis Factor/chemistry/*metabolism ; Recombinant Fusion Proteins/metabolism ; T-Lymphocytes/immunology ; Tetradecanoylphorbol Acetate/pharmacology ; Tumor Necrosis Factor-alpha/*metabolism
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  • 82
    Publication Date: 1994-03-04
    Description: The enzyme acetylcholinesterase generates a strong electrostatic field that can attract the cationic substrate acetylcholine to the active site. However, the long and narrow active site gorge seems inconsistent with the enzyme's high catalytic rate. A molecular dynamics simulation of acetylcholinesterase in water reveals the transient opening of a short channel, large enough to pass a water molecule, through a thin wall of the active site near tryptophan-84. This simulation suggests that substrate, products, or solvent could move through this "back door," in addition to the entrance revealed by the crystallographic structure. Electrostatic calculations show a strong field at the back door, oriented to attract the substrate and the reaction product choline and to repel the other reaction product, acetate. Analysis of the open back door conformation suggests a mutation that could seal the back door and thus test the hypothesis that thermal motion of this enzyme may open multiple routes of access to its active site.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gilson, M K -- Straatsma, T P -- McCammon, J A -- Ripoll, D R -- Faerman, C H -- Axelsen, P H -- Silman, I -- Sussman, J L -- New York, N.Y. -- Science. 1994 Mar 4;263(5151):1276-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Houston, TX 77204-5641.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8122110" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcholine/metabolism ; Acetylcholinesterase/*chemistry/metabolism ; Binding Sites ; Catalysis ; Choline/metabolism ; Computer Simulation ; Crystallography, X-Ray ; Electrochemistry ; Models, Molecular ; *Protein Conformation
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  • 83
    Publication Date: 1994-06-10
    Description: Specific protein-ligand interactions are critical for cellular function, and most proteins select their partners with sharp discrimination. However, the oligopeptide-binding protein of Salmonella typhimurium (OppA) binds peptides of two to five amino acid residues without regard to sequence. The crystal structure of OppA reveals a three-domain organization, unlike other periplasmic binding proteins. In OppA-peptide complexes, the ligands are completely enclosed in the protein interior, a mode of binding that normally imposes tight specificity. The protein fulfills the hydrogen bonding and electrostatic potential of the ligand main chain and accommodates the peptide side chains in voluminous hydrated cavities.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tame, J R -- Murshudov, G N -- Dodson, E J -- Neil, T K -- Dodson, G G -- Higgins, C F -- Wilkinson, A J -- New York, N.Y. -- Science. 1994 Jun 10;264(5165):1578-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of York, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8202710" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/chemistry/*metabolism ; Binding Sites ; Carrier Proteins/chemistry/*metabolism ; Crystallography, X-Ray ; Hydrogen Bonding ; Ligands ; Lipoproteins/chemistry/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Molecular Weight ; Oligopeptides/chemistry/*metabolism ; Protein Conformation ; Protein Structure, Secondary
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  • 84
    Publication Date: 1994-06-24
    Description: Structures of the 31-kilodalton catalytic domain of rat DNA polymerase beta (pol beta) and the whole 39-kilodalton enzyme were determined at 2.3 and 3.6 angstrom resolution, respectively. The 31-kilodalton domain is composed of fingers, palm, and thumb subdomains arranged to form a DNA binding channel reminiscent of the polymerase domains of the Klenow fragment of Escherichia coli DNA polymerase I, HIV-1 reverse transcriptase, and bacteriophage T7 RNA polymerase. The amino-terminal 8-kilodalton domain is attached to the fingers subdomain by a flexible hinge. The two invariant aspartates found in all polymerase sequences and implicated in catalytic activity have the same geometric arrangement within structurally similar but topologically distinct palms, indicating that the polymerases have maintained, or possibly re-evolved, a common nucleotidyl transfer mechanism. The location of Mn2+ and deoxyadenosine triphosphate in pol beta confirms the role of the invariant aspartates in metal ion and deoxynucleoside triphosphate binding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sawaya, M R -- Pelletier, H -- Kumar, A -- Wilson, S H -- Kraut, J -- CA17374/CA/NCI NIH HHS/ -- ES06839/ES/NIEHS NIH HHS/ -- GM10928/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1994 Jun 24;264(5167):1930-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of California, San Diego 92093-0317.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7516581" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Cloning, Molecular ; Crystallization ; Crystallography, X-Ray ; DNA/metabolism ; DNA Polymerase I/*chemistry/metabolism ; DNA-Directed RNA Polymerases/chemistry/metabolism ; Deoxyadenine Nucleotides/chemistry/metabolism ; Deoxycytosine Nucleotides/chemistry/metabolism ; Dideoxynucleotides ; HIV Reverse Transcriptase ; Protein Folding ; Protein Structure, Secondary ; RNA-Directed DNA Polymerase/chemistry/metabolism ; Rats ; Recombinant Proteins/chemistry ; Viral Proteins
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  • 85
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1994-10-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taubes, G -- New York, N.Y. -- Science. 1994 Oct 21;266(5184):364-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7939675" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Carbon Monoxide/chemistry ; Crystallization ; *Crystallography, X-Ray ; Motion Pictures as Topic ; Myoglobin/*chemistry ; Proteins/*chemistry ; Spectrophotometry/instrumentation/methods
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  • 86
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1994-02-18
    Description: Molecular chaperones of the Hsp70 type transiently sequester unfolded segments of proteins and promote their correct folding. Target peptides were labeled with an environmentally sensitive fluorophore so that their binding to the molecular chaperone DnaK of Escherichia coli could be followed in real time. The two-step process was characterized by relaxation times of 27 seconds and 200 seconds with 2 microM DnaK and 0.1 microM ligand at 25 degrees C. In the presence of adenosine triphosphate, the formation of the complex was greatly accelerated and appeared to be a single-exponential process with a relaxation time of 0.4 second. The binding-release cycle of DnaK thus occurs in the time range of polypeptide chain elongation and folding and is too fast to be stoichiometrically coupled to the adenosine triphosphatase activity of the chaperone (turnover number, 0.13 per minute at 30 degrees C).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmid, D -- Baici, A -- Gehring, H -- Christen, P -- New York, N.Y. -- Science. 1994 Feb 18;263(5149):971-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biochemisches Institut, Universitat Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8310296" target="_blank"〉PubMed〈/a〉
    Keywords: 2-Naphthylamine/analogs & derivatives ; Adenosine Triphosphatases/metabolism ; Adenosine Triphosphate/analogs & derivatives/pharmacology ; Amino Acid Sequence ; Aspartate Aminotransferases/metabolism ; Bacterial Proteins/*metabolism ; Binding Sites ; Enzyme Precursors/metabolism ; *Escherichia coli Proteins ; Fluorescent Dyes ; *HSP70 Heat-Shock Proteins ; Heat-Shock Proteins/*metabolism ; Kinetics ; Molecular Sequence Data ; Peptide Fragments/*metabolism
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  • 87
    Publication Date: 1994-11-18
    Description: Muscle enhancer factor-2A (MEF2A), a member of the MADS family, induced myogenic development when ectopically expressed in clones of nonmuscle cells of human clones, a function previously limited to the muscle basic helix-loop-helix (bHLH) proteins. During myogenesis, MEF2A and bHLH proteins cooperatively activate skeletal muscle genes and physically interact through the MADS domain of MEF2A and the three myogenic amino acids of the muscle bHLH proteins. Thus, skeletal myogenesis is mediated by two distinct families of mutually inducible and interactive muscle transcription factors, either of which can initiate the developmental cascade.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaushal, S -- Schneider, J W -- Nadal-Ginard, B -- Mahdavi, V -- New York, N.Y. -- Science. 1994 Nov 18;266(5188):1236-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cardiology, Children's Hospital, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7973707" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Cell Differentiation ; Cell Line ; DNA/metabolism ; DNA-Binding Proteins/genetics/*metabolism ; *Gene Expression Regulation ; Genes, Reporter ; Haplorhini ; Helix-Loop-Helix Motifs ; Humans ; MADS Domain Proteins ; MEF2 Transcription Factors ; Mice ; Molecular Sequence Data ; Muscle, Skeletal/*cytology/metabolism ; MyoD Protein/biosynthesis/*metabolism ; Myogenic Regulatory Factors ; Myogenin/biosynthesis/genetics/metabolism ; Transcription Factors/genetics/*metabolism ; Transfection
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  • 88
    Publication Date: 1994-11-04
    Description: The three-dimensional structure of a ternary complex of the purine repressor, PurR, bound to both its corepressor, hypoxanthine, and the 16-base pair purF operator site has been solved at 2.7 A resolution by x-ray crystallography. The bipartite structure of PurR consists of an amino-terminal DNA-binding domain and a larger carboxyl-terminal corepressor binding and dimerization domain that is similar to that of the bacterial periplasmic binding proteins. The DNA-binding domain contains a helix-turn-helix motif that makes base-specific contacts in the major groove of the DNA. Base contacts are also made by residues of symmetry-related alpha helices, the "hinge" helices, which bind deeply in the minor groove. Critical to hinge helix-minor groove binding is the intercalation of the side chains of Leu54 and its symmetry-related mate, Leu54', into the central CpG-base pair step. These residues thereby act as "leucine levers" to pry open the minor groove and kink the purF operator by 45 degrees.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schumacher, M A -- Choi, K Y -- Zalkin, H -- Brennan, R G -- GM 24658/GM/NIGMS NIH HHS/ -- GM 49244/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1994 Nov 4;266(5186):763-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland 97201-3098.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7973627" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/*chemistry/genetics/metabolism ; Base Sequence ; Binding Sites ; Computer Graphics ; Crystallography, X-Ray ; DNA/chemistry/*metabolism ; DNA-Binding Proteins/*chemistry/genetics/metabolism ; *Escherichia coli Proteins ; Hydrogen Bonding ; Hypoxanthine ; Hypoxanthines/metabolism ; Lac Repressors ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; *Operator Regions, Genetic ; Protein Conformation ; Protein Structure, Secondary ; Repressor Proteins/*chemistry/genetics/metabolism
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  • 89
    Publication Date: 1994-07-22
    Description: Cellulose is the major polysaccharide of plants where it plays a predominantly structural role. A variety of highly specialized microorganisms have evolved to produce enzymes that either synergistically or in complexes can carry out the complete hydrolysis of cellulose. The structure of the major cellobiohydrolase, CBHI, of the potent cellulolytic fungus Trichoderma reesei has been determined and refined to 1.8 angstrom resolution. The molecule contains a 40 angstrom long active site tunnel that may account for many of the previously poorly understood macroscopic properties of the enzyme and its interaction with solid cellulose. The active site residues were identified by solving the structure of the enzyme complexed with an oligosaccharide, o-iodobenzyl-1-thio-beta-cellobioside. The three-dimensional structure is very similar to a family of bacterial beta-glucanases with the main-chain topology of the plant legume lectins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Divne, C -- Stahlberg, J -- Reinikainen, T -- Ruohonen, L -- Pettersson, G -- Knowles, J K -- Teeri, T T -- Jones, T A -- New York, N.Y. -- Science. 1994 Jul 22;265(5171):524-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Uppsala University, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8036495" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Catalysis ; Cellobiose/analogs & derivatives/chemistry/metabolism ; Cellulose/metabolism ; Cellulose 1,4-beta-Cellobiosidase ; Computer Graphics ; Crystallography, X-Ray ; Glycoside Hydrolases/*chemistry/metabolism ; Hydrogen Bonding ; Iodobenzenes/chemistry/metabolism ; Models, Molecular ; Protein Structure, Secondary ; Trichoderma/*enzymology
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  • 90
    Publication Date: 1994-07-29
    Description: The Escherichia coli chaperonins GroEL and GroES facilitate protein folding in an adenosine triphosphate (ATP)-dependent manner. After a single cycle of ATP hydrolysis by the adenosine triphosphatase (ATPase) activity of GroEL, the bi-toroidal GroEL formed a stable asymmetric ternary complex with GroES and nucleotide (bulletlike structures). With each subsequent turnover, ATP was hydrolyzed by one ring of GroEL in a quantized manner, completely releasing the adenosine diphosphate and GroES that were tightly bound to the other ring as a result of the previous turnover. The catalytic cycle involved formation of a symmetric complex (football-like structures) as an intermediate that accumulated before the rate-determining hydrolytic step. After one to two cycles, most of the substrate protein dissociated still in a nonnative state, which is consistent with intermolecular transfer of the substrate protein between toroids of high and low affinity. A unifying model for chaperonin-facilitated protein folding based on successive rounds of binding and release, and partitioning between committed and kinetically trapped intermediates, is proposed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Todd, M J -- Viitanen, P V -- Lorimer, G H -- New York, N.Y. -- Science. 1994 Jul 29;265(5172):659-66.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉E. I. DuPont de Nemours and Company, Central Research and Development Department, Wilmington, DE 19880.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7913555" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/*metabolism ; Bacterial Proteins/*metabolism ; Binding Sites ; Chaperonin 10 ; Chaperonin 60 ; Heat-Shock Proteins/*metabolism ; Kinetics ; Models, Chemical ; *Protein Folding ; Ribulose-Bisphosphate Carboxylase/metabolism
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  • 91
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1994-07-29
    Description: In eukaryotic cells, a multitude of RNA-binding proteins play key roles in the posttranscriptional regulation of gene expression. Characterization of these proteins has led to the identification of several RNA-binding motifs, and recent experiments have begun to illustrate how several of them bind RNA. The significance of these interactions is reflected in the recent discoveries that several human and other vertebrate genetic disorders are caused by aberrant expression of RNA-binding proteins. The major RNA-binding motifs are described and examples of how they may function are given.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burd, C G -- Dreyfuss, G -- New York, N.Y. -- Science. 1994 Jul 29;265(5172):615-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia 19104-6148.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8036511" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Humans ; Molecular Sequence Data ; RNA-Binding Proteins/*chemistry/*physiology ; Ribonucleoproteins/chemistry ; Sequence Homology, Amino Acid
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  • 92
    Publication Date: 1994-12-23
    Description: HIV integrase is the enzyme responsible for inserting the viral DNA into the host chromosome; it is essential for HIV replication. The crystal structure of the catalytically active core domain (residues 50 to 212) of HIV-1 integrase was determined at 2.5 A resolution. The central feature of the structure is a five-stranded beta sheet flanked by helical regions. The overall topology reveals that this domain of integrase belongs to a superfamily of polynucleotidyl transferases that includes ribonuclease H and the Holliday junction resolvase RuvC. The active site region is identified by the position of two of the conserved carboxylate residues essential for catalysis, which are located at similar positions in ribonuclease H. In the crystal, two molecules form a dimer with a extensive solvent-inaccessible interface of 1300 A2 per monomer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dyda, F -- Hickman, A B -- Jenkins, T M -- Engelman, A -- Craigie, R -- Davies, D R -- New York, N.Y. -- Science. 1994 Dec 23;266(5193):1981-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Biology, NIDDK, NIH, Bethesda, MD 20892-0560.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7801124" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Crystallization ; Crystallography, X-Ray ; DNA Nucleotidyltransferases/*chemistry ; HIV-1/*enzymology ; Hydrogen Bonding ; Integrases ; Models, Molecular ; Molecular Sequence Data ; Protein Folding ; Protein Structure, Secondary ; Ribonuclease H/chemistry ; Solubility ; Virus Integration
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  • 93
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1994-10-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carr, C M -- Kim, P S -- New York, N.Y. -- Science. 1994 Oct 14;266(5183):234-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Cambridge, MA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7939658" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Membrane/metabolism/virology ; Endocytosis ; Endosomes/virology ; Hemagglutinin Glycoproteins, Influenza Virus ; Hemagglutinins, Viral/chemistry/*physiology ; Hydrogen-Ion Concentration ; *Membrane Fusion ; Models, Biological ; Models, Molecular ; Orthomyxoviridae/immunology/*physiology ; Protein Conformation ; Viral Envelope Proteins/chemistry/*physiology
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  • 94
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1994-05-20
    Description: In spite of the large amount of sequence conservation among the DNA binding segments of basic region leucine zipper (bZIP) proteins, these proteins can discriminate differently between target sequences that differ in half-site spacing. Here it is shown that the half-site spacing preferences of bZIP proteins are the result of (i) the differential intrinsic curvature in target binding sites that differ by insertion or deletion of a single base pair and (ii) the ability of some bZIP proteins to overcome this intrinsic curvature through a mechanism dependent on basic segment residues.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Paolella, D N -- Palmer, C R -- Schepartz, A -- New York, N.Y. -- Science. 1994 May 20;264(5162):1130-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Yale University, New Haven, CT 06511.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8178171" target="_blank"〉PubMed〈/a〉
    Keywords: Activating Transcription Factor 2 ; Amino Acid Sequence ; Base Sequence ; Basic-Leucine Zipper Transcription Factors ; Binding Sites ; Cyclic AMP Response Element-Binding Protein/chemistry/*metabolism ; DNA/chemistry/*metabolism ; DNA-Binding Proteins/chemistry/*metabolism ; Fungal Proteins/chemistry/*metabolism ; G-Box Binding Factors ; *Leucine Zippers ; Molecular Sequence Data ; Nucleic Acid Conformation ; Oligodeoxyribonucleotides/chemistry/metabolism ; Protein Kinases/chemistry/*metabolism ; Proto-Oncogene Proteins c-jun/chemistry/metabolism ; *Saccharomyces cerevisiae Proteins ; *Transcription Factors
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 95
    Publication Date: 1994-07-01
    Description: The Epstein-Barr virus (EBV) transactivator protein, termed Epstein-Barr virus nuclear antigen 2 (EBNA2), plays a critical role in the regulation of latent viral transcription and in the immortalization of EBV-infected B cells. Unlike most transcription factors, EBNA2 does not bind directly to its cis-responsive DNA element but requires a cellular factor, termed C-promoter binding factor 1 (CBF1). Here, CBF1 was purified and was found to directly interact with EBNA2. CBF1 is identical to a protein thought to be involved in immunoglobulin gene rearrangement, RBPJ kappa. Contrary to previous reports, CBF1-RBPJ kappa did not bind to the recombination signal sequences but instead bound to sites in the EBV C-promoter and in the CD23 promoter.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Henkel, T -- Ling, P D -- Hayward, S D -- Peterson, M G -- CA42245/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1994 Jul 1;265(5168):92-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Tularik Inc, South San Francisco, CA 94080.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8016657" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antigens, Viral/*genetics ; Base Sequence ; Binding Sites ; DNA-Binding Proteins/chemistry/*genetics/isolation & purification/*metabolism ; Epstein-Barr Virus Nuclear Antigens ; HeLa Cells ; Herpesvirus 4, Human/*genetics/immunology ; Humans ; Immunoglobulin J Recombination Signal Sequence-Binding Protein ; Molecular Sequence Data ; *Nuclear Proteins ; *Promoter Regions, Genetic ; Receptors, IgE/genetics ; Regulatory Sequences, Nucleic Acid ; *Transcriptional Activation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 96
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1994-02-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉von Hippel, P H -- GM-15792/GM/NIGMS NIH HHS/ -- GM-29158/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1994 Feb 11;263(5148):769-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biology, University of Oregon, Eugene 97403.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8303292" target="_blank"〉PubMed〈/a〉
    Keywords: Base Composition ; Base Sequence ; Crystallography, X-Ray ; DNA/chemistry/*metabolism ; DNA-Binding Proteins/chemistry/*metabolism ; Models, Molecular ; Protein Binding ; Protein Conformation ; Thermodynamics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 97
    Publication Date: 1994-04-15
    Description: The most frequently occurring resistance of Gram-negative bacteria against tetracyclines is triggered by drug recognition of the Tet repressor. This causes dissociation of the repressor-operator DNA complex and enables expression of the resistance protein TetA, which is responsible for active efflux of tetracycline. The 2.5 angstrom resolution crystal structure of the homodimeric Tet repressor complexed with tetracycline-magnesium reveals detailed drug recognition. The orientation of the operator-binding helix-turn-helix motifs of the repressor is inverted in comparison with other DNA binding proteins. The repressor-drug complex is unable to interact with DNA because the separation of the DNA binding motifs is 5 angstroms wider than usually observed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hinrichs, W -- Kisker, C -- Duvel, M -- Muller, A -- Tovar, K -- Hillen, W -- Saenger, W -- New York, N.Y. -- Science. 1994 Apr 15;264(5157):418-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Kristallographie, Freie Universitat Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8153629" target="_blank"〉PubMed〈/a〉
    Keywords: Antiporters/*chemistry/genetics/metabolism ; Bacterial Proteins/*chemistry/genetics/metabolism ; Crystallography, X-Ray ; DNA, Bacterial/metabolism ; Helix-Loop-Helix Motifs ; Hydrogen Bonding ; Magnesium/chemistry ; Models, Molecular ; Mutation ; Operator Regions, Genetic ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Repressor Proteins/*chemistry/genetics/metabolism ; Tetracycline/*chemistry/metabolism ; *Tetracycline Resistance/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 98
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1994-03-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Flam, F -- New York, N.Y. -- Science. 1994 Mar 18;263(5153):1563-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8128241" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Models, Molecular ; Protein Conformation ; *Protein Engineering ; *Protein Folding ; Protein Structure, Secondary
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 99
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1994-06-03
    Description: The plant hormone abscisic acid (ABA) mediates various responses such as stomatal closure, the maintenance of seed dormancy, and the inhibition of plant growth. All three responses are affected in the ABA-insensitive mutant abi1 of Arabidopsis thaliana, suggesting that an early step in the signaling of ABA is controlled by the ABI1 locus. The ABI1 gene was cloned by chromosome walking, and a missense mutation was identified in the structural gene of the abi1 mutant. The ABI1 gene encodes a protein with high similarity to protein serine or threonine phosphatases of type 2C with the novel feature of a putative Ca2+ binding site. Thus, the control of the phosphorylation state of cell signaling components by the ABI1 product could mediate pleiotropic hormone responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meyer, K -- Leube, M P -- Grill, E -- New York, N.Y. -- Science. 1994 Jun 3;264(5164):1452-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Plant Sciences, Swiss Federal Institute of Technology, Zurich.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8197457" target="_blank"〉PubMed〈/a〉
    Keywords: Abscisic Acid/*pharmacology ; Amino Acid Sequence ; Arabidopsis/enzymology/genetics/*metabolism ; *Arabidopsis Proteins ; Binding Sites ; Calcium/metabolism ; Chromosome Walking ; Cloning, Molecular ; Genes, Plant ; Genetic Markers ; Molecular Sequence Data ; Mutation ; Phosphoprotein Phosphatases/chemistry/genetics/*metabolism ; Plants, Genetically Modified ; *Signal Transduction
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1994-02-11
    Description: Thermodynamic studies have demonstrated the central importance of a large negative heat capacity change (delta C degree assoc) in site-specific protein-DNA recognition. Dissection of the large negative delta C degree assoc and the entropy change of protein-ligand and protein-DNA complexation provide a thermodynamic signature identifying processes in which local folding is coupled to binding. Estimates of the number of residues that fold on binding obtained from this analysis agree with structural data. Structural comparisons indicate that these local folding transitions create key parts of the protein-DNA interface. The energetic implications of this "induced fit" model for DNA site recognition are considered.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spolar, R S -- Record, M T Jr -- GM23467/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1994 Feb 11;263(5148):777-84.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Wisconsin-Madison 53706.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8303294" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; Crystallography, X-Ray ; DNA/chemistry/*metabolism ; DNA-Binding Proteins/chemistry/*metabolism ; Models, Molecular ; Nucleic Acid Conformation ; Protein Conformation ; *Protein Folding ; Thermodynamics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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