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  • Articles  (82)
  • Protein Conformation  (82)
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  • Articles  (82)
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  • American Association for the Advancement of Science (AAAS)  (82)
  • American Institute of Physics (AIP)
  • Oxford University Press
  • Springer Nature
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  • 2010-2014  (38)
  • 1995-1999  (44)
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  • 1
    Publication Date: 2013-11-23
    Description: Oxamniquine resistance evolved in the human blood fluke (Schistosoma mansoni) in Brazil in the 1970s. We crossed parental parasites differing ~500-fold in drug response, determined drug sensitivity and marker segregation in clonally derived second-generation progeny, and identified a single quantitative trait locus (logarithm of odds = 31) on chromosome 6. A sulfotransferase was identified as the causative gene by using RNA interference knockdown and biochemical complementation assays, and we subsequently demonstrated independent origins of loss-of-function mutations in field-derived and laboratory-selected resistant parasites. These results demonstrate the utility of linkage mapping in a human helminth parasite, while crystallographic analyses of protein-drug interactions illuminate the mode of drug action and provide a framework for rational design of oxamniquine derivatives that kill both S. mansoni and S. haematobium, the two species responsible for 〉99% of schistosomiasis cases worldwide.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136436/" 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/PMC4136436/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Valentim, Claudia L L -- Cioli, Donato -- Chevalier, Frederic D -- Cao, Xiaohang -- Taylor, Alexander B -- Holloway, Stephen P -- Pica-Mattoccia, Livia -- Guidi, Alessandra -- Basso, Annalisa -- Tsai, Isheng J -- Berriman, Matthew -- Carvalho-Queiroz, Claudia -- Almeida, Marcio -- Aguilar, Hector -- Frantz, Doug E -- Hart, P John -- LoVerde, Philip T -- Anderson, Timothy J C -- 098051/Wellcome Trust/United Kingdom -- 5R21-AI072704/AI/NIAID NIH HHS/ -- 5R21-AI096277/AI/NIAID NIH HHS/ -- C06 RR013556/RR/NCRR NIH HHS/ -- HHSN272201000005I/PHS HHS/ -- R01 AI097576/AI/NIAID NIH HHS/ -- R01-AI097576/AI/NIAID NIH HHS/ -- R21 AI072704/AI/NIAID NIH HHS/ -- R21 AI096277/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 13;342(6164):1385-9. doi: 10.1126/science.1243106. Epub 2013 Nov 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Biochemistry and Pathology, University of Texas Health Science Center, San Antonio, TX 78229, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24263136" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Drug Resistance/*genetics ; Gene Knockdown Techniques ; Genetic Linkage ; Helminth Proteins/*genetics ; Humans ; Molecular Sequence Data ; Mutation ; Oxamniquine/*pharmacology ; Phylogeny ; Protein Conformation ; Quantitative Trait Loci ; RNA Interference ; Schistosoma mansoni/*drug effects/*genetics ; Schistosomicides/*pharmacology ; Sulfotransferases/chemistry/classification/*genetics
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  • 2
    Publication Date: 2013-07-28
    Description: The essential bacterial protein FtsZ is a guanosine triphosphatase that self-assembles into a structure at the division site termed the "Z ring". During cytokinesis, the Z ring exerts a constrictive force on the membrane by using the chemical energy of guanosine triphosphate hydrolysis. However, the structural basis of this constriction remains unresolved. Here, we present the crystal structure of a guanosine diphosphate-bound Mycobacterium tuberculosis FtsZ protofilament, which exhibits a curved conformational state. The structure reveals a longitudinal interface that is important for function. The protofilament curvature highlights a hydrolysis-dependent conformational switch at the T3 loop that leads to longitudinal bending between subunits, which could generate sufficient force to drive cytokinesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816583/" 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/PMC3816583/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Ying -- Hsin, Jen -- Zhao, Lingyun -- Cheng, Yiwen -- Shang, Weina -- Huang, Kerwyn Casey -- Wang, Hong-Wei -- Ye, Sheng -- 1F32GM100677-01A1/GM/NIGMS NIH HHS/ -- DP2 OD006466/OD/NIH HHS/ -- DP2OD006466/OD/NIH HHS/ -- F32 GM100677/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jul 26;341(6144):392-5. doi: 10.1126/science.1239248.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Life Sciences Institute, Zhejiang University, Hangzhou, 310058 Zhejiang, P.R. China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23888039" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/*chemistry/genetics/*metabolism ; Cell Membrane/physiology ; Crystallography, X-Ray ; *Cytokinesis ; Cytoskeletal Proteins/*chemistry/genetics/*metabolism ; Escherichia coli/chemistry ; Guanosine Diphosphate/chemistry/metabolism ; Guanosine Triphosphate/metabolism ; Hydrolysis ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Mycobacterium tuberculosis/*chemistry/physiology ; Point Mutation ; Protein Conformation ; Protein Multimerization ; Protein Subunits/chemistry/metabolism ; Staphylococcus aureus/chemistry
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  • 3
    Publication Date: 2013-09-28
    Description: The protein density and arrangement of subunits of a complete, 32-protein, RNA polymerase II (pol II) transcription pre-initiation complex (PIC) were determined by means of cryogenic electron microscopy and a combination of chemical cross-linking and mass spectrometry. The PIC showed a marked division in two parts, one containing all the general transcription factors (GTFs) and the other pol II. Promoter DNA was associated only with the GTFs, suspended above the pol II cleft and not in contact with pol II. This structural principle of the PIC underlies its conversion to a transcriptionally active state; the PIC is poised for the formation of a transcription bubble and descent of the DNA into the pol II cleft.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039082/" 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/PMC4039082/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murakami, Kenji -- Elmlund, Hans -- Kalisman, Nir -- Bushnell, David A -- Adams, Christopher M -- Azubel, Maia -- Elmlund, Dominika -- Levi-Kalisman, Yael -- Liu, Xin -- Gibbons, Brian J -- Levitt, Michael -- Kornberg, Roger D -- AI21144/AI/NIAID NIH HHS/ -- GM063817/GM/NIGMS NIH HHS/ -- GM49885/GM/NIGMS NIH HHS/ -- R01 AI021144/AI/NIAID NIH HHS/ -- R01 GM036659/GM/NIGMS NIH HHS/ -- R01 GM063817/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 8;342(6159):1238724. doi: 10.1126/science.1238724. Epub 2013 Sep 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24072820" target="_blank"〉PubMed〈/a〉
    Keywords: Cryoelectron Microscopy ; DNA, Fungal/chemistry/genetics ; *Gene Expression Regulation, Fungal ; Multiprotein Complexes/*chemistry ; Nucleic Acid Conformation ; Protein Conformation ; RNA Polymerase II/*chemistry ; Saccharomyces cerevisiae/*enzymology/genetics ; Saccharomyces cerevisiae Proteins/*chemistry ; Transcription Factors, General/*chemistry ; *Transcription Initiation, Genetic
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  • 4
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-12-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉New York, N.Y. -- Science. 2013 Dec 20;342(6165):1442-3. doi: 10.1126/science.342.6165.1442-a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24357293" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Viral/chemistry/immunology ; *Drug Design ; Humans ; Infant ; Protein Conformation ; Protein Engineering ; Respiratory Syncytial Virus Infections/*prevention & control ; Respiratory Syncytial Virus Vaccines/*chemistry/immunology ; Respiratory Syncytial Viruses/*chemistry/immunology ; Viral Fusion Proteins/*chemistry/immunology ; X-Ray Diffraction
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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-02-23
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633482/" 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/PMC3633482/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ward, Andrew B -- Sali, Andrej -- Wilson, Ian A -- P01 AI082362/AI/NIAID NIH HHS/ -- U54 GM094586/GM/NIGMS NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 22;339(6122):913-5. doi: 10.1126/science.1228565.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, International AIDS Vaccine Initiative Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92037, USA. abward@scripps.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23430643" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Bacterial Secretion Systems ; Biochemistry/*methods ; Chromatin/chemistry ; Computational Biology ; Macromolecular Substances/*chemistry ; *Models, Molecular ; Molecular Biology/*methods ; Molecular Structure ; Multiprotein Complexes/*chemistry ; Proteasome Endopeptidase Complex/chemistry ; Protein Conformation ; Proteins/*chemistry ; Software
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  • 6
    Publication Date: 2013-11-30
    Description: In photosynthetic organisms, photons are captured by light-harvesting antenna complexes, and energy is transferred to reaction centers where photochemical reactions take place. We describe here the isolation and characterization of a fully functional megacomplex composed of a phycobilisome antenna complex and photosystems I and II from the cyanobacterium Synechocystis PCC 6803. A combination of in vivo protein cross-linking, mass spectrometry, and time-resolved spectroscopy indicates that the megacomplex is organized to facilitate energy transfer but not intercomplex electron transfer, which requires diffusible intermediates and the cytochrome b6f complex. The organization provides a basis for understanding how phycobilisomes transfer excitation energy to reaction centers and how the energy balance of two photosystems is achieved, allowing the organism to adapt to varying ecophysiological conditions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3947847/" 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/PMC3947847/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Haijun -- Zhang, Hao -- Niedzwiedzki, Dariusz M -- Prado, Mindy -- He, Guannan -- Gross, Michael L -- Blankenship, Robert E -- 8 P41 GM103422-35/GM/NIGMS NIH HHS/ -- P41 GM103422/GM/NIGMS NIH HHS/ -- P41 RR000954/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 29;342(6162):1104-7. doi: 10.1126/science.1242321.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Washington University in St. Louis, St. Louis, MO 63130, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24288334" target="_blank"〉PubMed〈/a〉
    Keywords: Cross-Linking Reagents/chemistry ; Energy Transfer ; Fluorescence ; *Photosynthesis ; Photosystem I Protein Complex/*chemistry/genetics/isolation & purification ; Photosystem II Protein Complex/*chemistry/genetics/isolation & purification ; Phycobilisomes/*chemistry/genetics/isolation & purification ; Protein Conformation ; Synechocystis/*enzymology
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  • 7
    Publication Date: 2013-06-08
    Description: Genome-scale network reconstruction has enabled predictive modeling of metabolism for many systems. Traditionally, protein structural information has not been represented in such reconstructions. Expansion of a genome-scale model of Escherichia coli metabolism by including experimental and predicted protein structures enabled the analysis of protein thermostability in a network context. This analysis allowed the prediction of protein activities that limit network function at superoptimal temperatures and mechanistic interpretations of mutations found in strains adapted to heat. Predicted growth-limiting factors for thermotolerance were validated through nutrient supplementation experiments and defined metabolic sensitivities to heat stress, providing evidence that metabolic enzyme thermostability is rate-limiting at superoptimal temperatures. Inclusion of structural information expanded the content and predictive capability of genome-scale metabolic networks that enable structural systems biology of metabolism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777776/" 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/PMC3777776/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chang, Roger L -- Andrews, Kathleen -- Kim, Donghyuk -- Li, Zhanwen -- Godzik, Adam -- Palsson, Bernhard O -- R01 GM057089/GM/NIGMS NIH HHS/ -- R01 GM101457/GM/NIGMS NIH HHS/ -- R01GM101457/GM/NIGMS NIH HHS/ -- U54 GM094586/GM/NIGMS NIH HHS/ -- U54GM094586/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jun 7;340(6137):1220-3. doi: 10.1126/science.1234012.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, CA 92093-0412, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744946" target="_blank"〉PubMed〈/a〉
    Keywords: Escherichia coli/*genetics/growth & development/*metabolism ; Escherichia coli Proteins/chemistry/genetics/*metabolism ; Gene Expression Regulation, Bacterial ; *Hot Temperature ; *Metabolic Networks and Pathways ; Models, Biological ; Protein Conformation ; Systems Biology ; Transcriptional Activation
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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-11-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Malik, Sohail -- Roeder, Robert G -- New York, N.Y. -- Science. 2013 Nov 8;342(6159):706-7. doi: 10.1126/science.1246170.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biochemistry and Molecular Biology, Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24202169" target="_blank"〉PubMed〈/a〉
    Keywords: Catalytic Domain ; Cryoelectron Microscopy ; Crystallography ; DNA/*chemistry ; Humans ; *Promoter Regions, Genetic ; Protein Conformation ; RNA Polymerase II/*chemistry ; Transcription Factors, General/*chemistry ; *Transcription Initiation, Genetic
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  • 9
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-06-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sharon, Michal -- New York, N.Y. -- Science. 2013 May 31;340(6136):1059-60. doi: 10.1126/science.1236303.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel. michal.sharon@weizmann.ac.il〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23723227" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Mass Spectrometry/*methods ; Microscopy, Electron ; Nuclear Magnetic Resonance, Biomolecular ; Protein Conformation ; Proteins/*chemistry
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  • 10
    Publication Date: 2013-09-07
    Description: An avian-origin human-infecting influenza (H7N9) virus was recently identified in China. We have evaluated the viral hemagglutinin (HA) receptor-binding properties of two human H7N9 isolates, A/Shanghai/1/2013 (SH-H7N9) (containing the avian-signature residue Gln(226)) and A/Anhui/1/2013 (AH-H7N9) (containing the mammalian-signature residue Leu(226)). We found that SH-H7N9 HA preferentially binds the avian receptor analog, whereas AH-H7N9 HA binds both avian and human receptor analogs. Furthermore, an AH-H7N9 mutant HA (Leu(226) --〉 Gln) was found to exhibit dual receptor-binding property, indicating that other amino acid substitutions contribute to the receptor-binding switch. The structures of SH-H7N9 HA, AH-H7N9 HA, and its mutant in complex with either avian or human receptor analogs show how AH-H7N9 can bind human receptors while still retaining the avian receptor-binding property.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shi, Yi -- Zhang, Wei -- Wang, Fei -- Qi, Jianxun -- Wu, Ying -- Song, Hao -- Gao, Feng -- Bi, Yuhai -- Zhang, Yanfang -- Fan, Zheng -- Qin, Chengfeng -- Sun, Honglei -- Liu, Jinhua -- Haywood, Joel -- Liu, Wenjun -- Gong, Weimin -- Wang, Dayan -- Shu, Yuelong -- Wang, Yu -- Yan, Jinghua -- Gao, George F -- New York, N.Y. -- Science. 2013 Oct 11;342(6155):243-7. doi: 10.1126/science.1242917. Epub 2013 Sep 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24009358" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Birds ; Crystallography, X-Ray ; Glycine/chemistry/genetics/metabolism ; Hemagglutinin Glycoproteins, Influenza Virus/*chemistry/metabolism ; Humans ; Influenza A virus/*metabolism ; Influenza in Birds/*virology ; Influenza, Human/*virology ; Protein Conformation ; Receptors, Cell Surface/*chemistry/genetics/metabolism
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  • 11
    Publication Date: 2013-03-23
    Description: Biological membrane fission requires protein-driven stress. The guanosine triphosphatase (GTPase) dynamin builds up membrane stress by polymerizing into a helical collar that constricts the neck of budding vesicles. How this curvature stress mediates nonleaky membrane remodeling is actively debated. Using lipid nanotubes as substrates to directly measure geometric intermediates of the fission pathway, we found that GTP hydrolysis limits dynamin polymerization into short, metastable collars that are optimal for fission. Collars as short as two rungs translated radial constriction to reversible hemifission via membrane wedging of the pleckstrin homology domains (PHDs) of dynamin. Modeling revealed that tilting of the PHDs to conform with membrane deformations creates the low-energy pathway for hemifission. This local coordination of dynamin and lipids suggests how membranes can be remodeled in cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3980720/" 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/PMC3980720/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shnyrova, Anna V -- Bashkirov, Pavel V -- Akimov, Sergey A -- Pucadyil, Thomas J -- Zimmerberg, Joshua -- Schmid, Sandra L -- Frolov, Vadim A -- GM42455/GM/NIGMS NIH HHS/ -- R01 GM042455/GM/NIGMS NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 Mar 22;339(6126):1433-6. doi: 10.1126/science.1233920.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biophysics Unit (CSIC, UPV/EHU) and Department of Biochemistry and Molecular Biology, University of the Basque Country, Leioa, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23520112" target="_blank"〉PubMed〈/a〉
    Keywords: Biocatalysis ; Dynamin I/*chemistry/*metabolism ; Guanosine Triphosphate/metabolism ; Hydrolysis ; Lipid Bilayers/chemistry/*metabolism ; Models, Biological ; Nanotubes ; Protein Conformation ; Protein Multimerization ; Protein Structure, Tertiary ; Thermodynamics
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  • 12
    Publication Date: 2013-03-23
    Description: Serotonin or 5-hydroxytryptamine (5-HT) regulates a wide spectrum of human physiology through the 5-HT receptor family. We report the crystal structures of the human 5-HT1B G protein-coupled receptor bound to the agonist antimigraine medications ergotamine and dihydroergotamine. The structures reveal similar binding modes for these ligands, which occupy the orthosteric pocket and an extended binding pocket close to the extracellular loops. The orthosteric pocket is formed by residues conserved in the 5-HT receptor family, clarifying the family-wide agonist activity of 5-HT. Compared with the structure of the 5-HT2B receptor, the 5-HT1B receptor displays a 3 angstrom outward shift at the extracellular end of helix V, resulting in a more open extended pocket that explains subtype selectivity. Together with docking and mutagenesis studies, these structures provide a comprehensive structural basis for understanding receptor-ligand interactions and designing subtype-selective serotonergic drugs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644373/" 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/PMC3644373/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Chong -- Jiang, Yi -- Ma, Jinming -- Wu, Huixian -- Wacker, Daniel -- Katritch, Vsevolod -- Han, Gye Won -- Liu, Wei -- Huang, Xi-Ping -- Vardy, Eyal -- McCorvy, John D -- Gao, Xiang -- Zhou, X Edward -- Melcher, Karsten -- Zhang, Chenghai -- Bai, Fang -- Yang, Huaiyu -- Yang, Linlin -- Jiang, Hualiang -- Roth, Bryan L -- Cherezov, Vadim -- Stevens, Raymond C -- Xu, H Eric -- P50 GM073197/GM/NIGMS NIH HHS/ -- R01 DA027170/DA/NIDA NIH HHS/ -- R01 DA27170/DA/NIDA NIH HHS/ -- R01 DK071662/DK/NIDDK NIH HHS/ -- R01 MH061887/MH/NIMH NIH HHS/ -- R01 MH61887/MH/NIMH NIH HHS/ -- U19 MH082441/MH/NIMH NIH HHS/ -- U19 MH82441/MH/NIMH 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. 2013 May 3;340(6132):610-4. doi: 10.1126/science.1232807. Epub 2013 Mar 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational 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/23519210" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Crystallography, X-Ray ; Dihydroergotamine/chemistry/*metabolism ; Ergotamine/chemistry/*metabolism ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Lysergic Acid Diethylamide/chemistry/metabolism ; Models, Molecular ; Molecular Docking Simulation ; Molecular Sequence Data ; Mutagenesis ; Norfenfluramine/chemistry/metabolism ; Pindolol/analogs & derivatives/chemistry/metabolism ; Propranolol/chemistry/metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Receptor, Serotonin, 5-HT1B/*chemistry/genetics/*metabolism ; Serotonin 5-HT1 Receptor Agonists/*chemistry/*metabolism ; Tryptamines/chemistry/metabolism
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  • 13
    Publication Date: 2013-08-31
    Description: MraY (phospho-MurNAc-pentapeptide translocase) is an integral membrane enzyme that catalyzes an essential step of bacterial cell wall biosynthesis: the transfer of the peptidoglycan precursor phospho-MurNAc-pentapeptide to the lipid carrier undecaprenyl phosphate. MraY has long been considered a promising target for the development of antibiotics, but the lack of a structure has hindered mechanistic understanding of this critical enzyme and the enzyme superfamily in general. The superfamily includes enzymes involved in bacterial lipopolysaccharide/teichoic acid formation and eukaryotic N-linked glycosylation, modifications that are central in many biological processes. We present the crystal structure of MraY from Aquifex aeolicus (MraYAA) at 3.3 A resolution, which allows us to visualize the overall architecture, locate Mg(2+) within the active site, and provide a structural basis of catalysis for this class of enzyme.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906829/" 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/PMC3906829/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chung, Ben C -- Zhao, Jinshi -- Gillespie, Robert A -- Kwon, Do-Yeon -- Guan, Ziqiang -- Hong, Jiyong -- Zhou, Pei -- Lee, Seok-Yong -- AI-55588/AI/NIAID NIH HHS/ -- GM-069338/GM/NIGMS NIH HHS/ -- GM-51310/GM/NIGMS NIH HHS/ -- R01 AI055588/AI/NIAID NIH HHS/ -- R01 GM051310/GM/NIGMS NIH HHS/ -- R01 GM100984/GM/NIGMS NIH HHS/ -- U54 GM069338/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Aug 30;341(6149):1012-6. doi: 10.1126/science.1236501.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23990562" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteria/*enzymology ; Bacterial Proteins/*chemistry/genetics ; Catalytic Domain ; Cell Wall/*chemistry/enzymology ; Crystallography, X-Ray ; Cytoplasm/enzymology ; Membrane Proteins/*chemistry/genetics ; Periplasm/enzymology ; Protein Conformation ; Protein Structure, Secondary ; Transferases/*chemistry/genetics
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  • 14
    Publication Date: 2013-03-23
    Description: Toll-like receptor 7 (TLR7) and TLR8 recognize single-stranded RNA and initiate innate immune responses. Several synthetic agonists of TLR7-TLR8 display novel therapeutic potential; however, the molecular basis for ligand recognition and activation of signaling by TLR7 or TLR8 is largely unknown. In this study, the crystal structures of unliganded and ligand-induced activated human TLR8 dimers were elucidated. Ligand recognition was mediated by a dimerization interface formed by two protomers. Upon ligand stimulation, the TLR8 dimer was reorganized such that the two C termini were brought into proximity. The loop between leucine-rich repeat 14 (LRR14) and LRR15 was cleaved; however, the N- and C-terminal halves remained associated and contributed to ligand recognition and dimerization. Thus, ligand binding induces reorganization of the TLR8 dimer, which enables downstream signaling processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tanji, Hiromi -- Ohto, Umeharu -- Shibata, Takuma -- Miyake, Kensuke -- Shimizu, Toshiyuki -- New York, N.Y. -- Science. 2013 Mar 22;339(6126):1426-9. doi: 10.1126/science.1229159.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23520111" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Crystallography, X-Ray ; Humans ; Hydrogen Bonding ; Imidazoles/chemistry/*metabolism ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/chemistry/metabolism ; Protein Binding ; Protein Conformation ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Quinolines/chemistry/*metabolism ; Signal Transduction ; Thiazoles/chemistry/*metabolism ; Toll-Like Receptor 8/*agonists/*chemistry/metabolism
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  • 15
    Publication Date: 2013-05-25
    Description: The introduction of sulfa drugs for the chemotherapy of bacterial infections in 1935 revolutionized medicine. Although their mechanism of action is understood, the molecular bases for most of their side effects remain obscure. Here, we report that sulfamethoxazole and other sulfa drugs interfere with tetrahydrobiopterin biosynthesis through inhibition of sepiapterin reductase. Crystal structures of sepiapterin reductase with bound sulfa drugs reveal how structurally diverse sulfa drugs achieve specific inhibition of the enzyme. The effect of sulfa drugs on tetrahydrobiopterin-dependent neurotransmitter biosynthesis in cell-based assays provides a rationale for some of their central nervous system-related side effects, particularly in high-dose sulfamethoxazole therapy of Pneumocystis pneumonia. Our findings reveal an unexpected aspect of the pharmacology of sulfa drugs and might translate into their improved medical use.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haruki, Hirohito -- Pedersen, Miriam Gronlund -- Gorska, Katarzyna Irena -- Pojer, Florence -- Johnsson, Kai -- New York, N.Y. -- Science. 2013 May 24;340(6135):987-91. doi: 10.1126/science.1232972.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉EPFL, Institute of Chemical Sciences and Engineering, Institute of Bioengineering, National Centre of Competence in Research in Chemical Biology, 1015 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23704574" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Hydroxytryptophan/biosynthesis ; Adult ; Alcohol Oxidoreductases/*antagonists & inhibitors/*chemistry ; Anti-Infective Agents/adverse effects/*pharmacology/therapeutic use ; Biopterin/*analogs & derivatives/biosynthesis ; Cell Line ; Central Nervous System/drug effects ; Crystallography, X-Ray ; Fibroblasts/drug effects/metabolism ; Humans ; Levodopa/biosynthesis ; NADP/chemistry ; Nausea/chemically induced ; Pneumonia, Pneumocystis/drug therapy ; Protein Conformation ; Structure-Activity Relationship ; Sulfamethoxazole/adverse effects/*pharmacology/therapeutic use ; Trimethoprim, Sulfamethoxazole Drug Combination/pharmacology/therapeutic use ; Vomiting/chemically induced
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  • 16
    Publication Date: 2013-12-07
    Description: Host cell factor-1 (HCF-1), a transcriptional co-regulator of human cell-cycle progression, undergoes proteolytic maturation in which any of six repeated sequences is cleaved by the nutrient-responsive glycosyltransferase, O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). We report that the tetratricopeptide-repeat domain of O-GlcNAc transferase binds the carboxyl-terminal portion of an HCF-1 proteolytic repeat such that the cleavage region lies in the glycosyltransferase active site above uridine diphosphate-GlcNAc. The conformation is similar to that of a glycosylation-competent peptide substrate. Cleavage occurs between cysteine and glutamate residues and results in a pyroglutamate product. Conversion of the cleavage site glutamate into serine converts an HCF-1 proteolytic repeat into a glycosylation substrate. Thus, protein glycosylation and HCF-1 cleavage occur in the same active site.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930058/" 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/PMC3930058/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lazarus, Michael B -- Jiang, Jiaoyang -- Kapuria, Vaibhav -- Bhuiyan, Tanja -- Janetzko, John -- Zandberg, Wesley F -- Vocadlo, David J -- Herr, Winship -- Walker, Suzanne -- R01 GM094263/GM/NIGMS NIH HHS/ -- R01GM094263/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 6;342(6163):1235-9. doi: 10.1126/science.1243990.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24311690" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Substitution ; Catalytic Domain ; Crystallography, X-Ray ; Glycosylation ; Host Cell Factor C1/*chemistry/*metabolism ; Humans ; Hydrogen Bonding ; Models, Molecular ; N-Acetylglucosaminyltransferases/*chemistry/*metabolism ; Protein Conformation ; Protein Structure, Tertiary ; Proteolysis ; Pyrrolidonecarboxylic Acid/metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Uridine Diphosphate N-Acetylglucosamine/chemistry/metabolism
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  • 17
    Publication Date: 2013-03-30
    Description: Mutations in the nuclear membrane zinc metalloprotease ZMPSTE24 lead to diseases of lamin processing (laminopathies), such as the premature aging disease progeria and metabolic disorders. ZMPSTE24 processes prelamin A, a component of the nuclear lamina intermediate filaments, by cleaving it at two sites. Failure of this processing results in accumulation of farnesylated, membrane-associated prelamin A. The 3.4 angstrom crystal structure of human ZMPSTE24 has a seven transmembrane alpha-helical barrel structure, surrounding a large, water-filled, intramembrane chamber, capped by a zinc metalloprotease domain with the catalytic site facing into the chamber. The 3.8 angstrom structure of a complex with a CSIM tetrapeptide showed that the mode of binding of the substrate resembles that of an insect metalloprotease inhibitor in thermolysin. Laminopathy-associated mutations predicted to reduce ZMPSTE24 activity map to the zinc metalloprotease peptide-binding site and to the bottom of the chamber.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Quigley, Andrew -- Dong, Yin Yao -- Pike, Ashley C W -- Dong, Liang -- Shrestha, Leela -- Berridge, Georgina -- Stansfeld, Phillip J -- Sansom, Mark S P -- Edwards, Aled M -- Bountra, Chas -- von Delft, Frank -- Bullock, Alex N -- Burgess-Brown, Nicola A -- Carpenter, Elisabeth P -- 092809/Wellcome Trust/United Kingdom -- Canadian Institutes of Health Research/Canada -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Mar 29;339(6127):1604-7. doi: 10.1126/science.1231513.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Genomics Consortium, University of Oxford, Oxford, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23539603" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Catalytic Domain ; Crystallography, X-Ray ; Humans ; Lamin Type A ; Membrane Proteins/*chemistry/genetics ; Metabolism, Inborn Errors/genetics/*metabolism ; Metalloendopeptidases/*chemistry/genetics ; Molecular Sequence Data ; Nuclear Proteins/chemistry/genetics/*metabolism ; Progeria/genetics/metabolism ; Protein Conformation ; Protein Precursors/chemistry/genetics/*metabolism ; Substrate Specificity ; Thermolysin/chemistry
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  • 18
    Publication Date: 2013-04-13
    Description: Scaffold-assisted signaling cascades guide cellular decision-making. In budding yeast, one such signal transduction pathway called the mitotic exit network (MEN) governs the transition from mitosis to the G1 phase of the cell cycle. The MEN is conserved and in metazoans is known as the Hippo tumor-suppressor pathway. We found that signaling through the MEN kinase cascade was mediated by an unusual two-step process. The MEN kinase Cdc15 first phosphorylated the scaffold Nud1. This created a phospho-docking site on Nud1, to which the effector kinase complex Dbf2-Mob1 bound through a phosphoserine-threonine binding domain, in order to be activated by Cdc15. This mechanism of pathway activation has implications for signal transmission through other kinase cascades and might represent a general principle in scaffold-assisted signaling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884217/" 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/PMC3884217/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rock, Jeremy M -- Lim, Daniel -- Stach, Lasse -- Ogrodowicz, Roksana W -- Keck, Jamie M -- Jones, Michele H -- Wong, Catherine C L -- Yates, John R 3rd -- Winey, Mark -- Smerdon, Stephen J -- Yaffe, Michael B -- Amon, Angelika -- CA112967/CA/NCI NIH HHS/ -- ES015339/ES/NIEHS NIH HHS/ -- F32 GM086038/GM/NIGMS NIH HHS/ -- GM056800/GM/NIGMS NIH HHS/ -- GM51312/GM/NIGMS NIH HHS/ -- MC_U117584228/Medical Research Council/United Kingdom -- P30 CA014051/CA/NCI NIH HHS/ -- P41 GM103533/GM/NIGMS NIH HHS/ -- P41 RR011823/RR/NCRR NIH HHS/ -- R01 ES015339/ES/NIEHS NIH HHS/ -- R01 GM051312/GM/NIGMS NIH HHS/ -- R01 GM056800/GM/NIGMS NIH HHS/ -- R29 GM056800/GM/NIGMS NIH HHS/ -- U117584228/Medical Research Council/United Kingdom -- U54 CA112967/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 May 17;340(6134):871-5. doi: 10.1126/science.1235822. Epub 2013 Apr 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23579499" target="_blank"〉PubMed〈/a〉
    Keywords: Anaphase ; Cell Cycle Proteins/chemistry/*metabolism ; Deoxyribonucleases/chemistry/*metabolism ; Enzyme Activation ; GTP-Binding Proteins/*metabolism ; *Mitosis ; Phosphoproteins/chemistry/*metabolism ; Phosphorylation ; Protein Conformation ; Protein-Serine-Threonine Kinases/*metabolism ; Saccharomyces cerevisiae/cytology/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/*metabolism ; Signal Transduction ; tRNA Methyltransferases/chemistry/*metabolism
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  • 19
    Publication Date: 2013-01-05
    Description: The ubiquitin system regulates virtually all aspects of cellular function. We report a method to target the myriad enzymes that govern ubiquitination of protein substrates. We used massively diverse combinatorial libraries of ubiquitin variants to develop inhibitors of four deubiquitinases (DUBs) and analyzed the DUB-inhibitor complexes with crystallography. We extended the selection strategy to the ubiquitin conjugating (E2) and ubiquitin ligase (E3) enzymes and found that ubiquitin variants can also enhance enzyme activity. Last, we showed that ubiquitin variants can bind selectively to ubiquitin-binding domains. Ubiquitin variants exhibit selective function in cells and thus enable orthogonal modulation of specific enzymatic steps in the ubiquitin system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815447/" 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/PMC3815447/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ernst, Andreas -- Avvakumov, George -- Tong, Jiefei -- Fan, Yihui -- Zhao, Yanling -- Alberts, Philipp -- Persaud, Avinash -- Walker, John R -- Neculai, Ana-Mirela -- Neculai, Dante -- Vorobyov, Andrew -- Garg, Pankaj -- Beatty, Linda -- Chan, Pak-Kei -- Juang, Yu-Chi -- Landry, Marie-Claude -- Yeh, Christina -- Zeqiraj, Elton -- Karamboulas, Konstantina -- Allali-Hassani, Abdellah -- Vedadi, Masoud -- Tyers, Mike -- Moffat, Jason -- Sicheri, Frank -- Pelletier, Laurence -- Durocher, Daniel -- Raught, Brian -- Rotin, Daniela -- Yang, Jianhua -- Moran, Michael F -- Dhe-Paganon, Sirano -- Sidhu, Sachdev S -- 092076/Wellcome Trust/United Kingdom -- 092381/Wellcome Trust/United Kingdom -- 1R01NS072420-01/Canadian Institutes of Health Research/Canada -- MOP-102536/Canadian Institutes of Health Research/Canada -- MOP-111149/Canadian Institutes of Health Research/Canada -- MOP-13494/Canadian Institutes of Health Research/Canada -- MOP-57795/Canadian Institutes of Health Research/Canada -- R01 NS072420/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2013 Feb 1;339(6119):590-5. doi: 10.1126/science.1230161. Epub 2013 Jan 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23287719" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Combinatorial Chemistry Techniques ; Conserved Sequence ; Drug Design ; Endopeptidases/chemistry/*metabolism ; HEK293 Cells ; Humans ; Molecular Sequence Data ; Protease Inhibitors/chemistry/*isolation & purification/pharmacology ; Protein Conformation ; Protein Structure, Secondary ; Small Molecule Libraries ; Ubiquitin/chemistry/genetics/*metabolism ; Ubiquitin Thiolesterase/chemistry/*metabolism ; Ubiquitin-Conjugating Enzymes/chemistry/metabolism ; Ubiquitin-Protein Ligases/chemistry/metabolism ; Ubiquitination/*drug effects
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  • 20
    Publication Date: 2013-11-10
    Description: The last step in eukaryotic translational initiation involves the joining of the large and small subunits of the ribosome, with initiator transfer RNA (Met-tRNA(i)(Met)) positioned over the start codon of messenger RNA in the P site. This step is catalyzed by initiation factor eIF5B. We used recent advances in cryo-electron microscopy (cryo-EM) to determine a structure of the eIF5B initiation complex to 6.6 angstrom resolution from 〈3% of the population, comprising just 5143 particles. The structure reveals conformational changes in eIF5B, initiator tRNA, and the ribosome that provide insights into the role of eIF5B in translational initiation. The relatively high resolution obtained from such a small fraction of a heterogeneous sample suggests a general approach for characterizing the structure of other dynamic or transient biological complexes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836175/" 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/PMC3836175/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fernandez, Israel S -- Bai, Xiao-Chen -- Hussain, Tanweer -- Kelley, Ann C -- Lorsch, Jon R -- Ramakrishnan, V -- Scheres, Sjors H W -- 096570/Wellcome Trust/United Kingdom -- MC_U105184332/Medical Research Council/United Kingdom -- MC_UP_A025_1013/Medical Research Council/United Kingdom -- WT096570/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 Nov 15;342(6160):1240585. doi: 10.1126/science.1240585. Epub 2013 Nov 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24200810" target="_blank"〉PubMed〈/a〉
    Keywords: Analytic Sample Preparation Methods ; Cryoelectron Microscopy/methods ; Eukaryotic Initiation Factors/*chemistry ; Humans ; *Peptide Chain Initiation, Translational ; Protein Conformation ; RNA, Transfer, Met/chemistry ; Ribosomes/*chemistry ; Saccharomyces cerevisiae
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  • 21
    Publication Date: 2013-04-13
    Description: An ability to mimic the boundaries of biological compartments would improve our understanding of self-assembly and provide routes to new materials for the delivery of drugs and biologicals and the development of protocells. We show that short designed peptides can be combined to form unilamellar spheres approximately 100 nanometers in diameter. The design comprises two, noncovalent, heterodimeric and homotrimeric coiled-coil bundles. These are joined back to back to render two complementary hubs, which when mixed form hexagonal networks that close to form cages. This design strategy offers control over chemistry, self-assembly, reversibility, and size of such particles.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fletcher, Jordan M -- Harniman, Robert L -- Barnes, Frederick R H -- Boyle, Aimee L -- Collins, Andrew -- Mantell, Judith -- Sharp, Thomas H -- Antognozzi, Massimo -- Booth, Paula J -- Linden, Noah -- Miles, Mervyn J -- Sessions, Richard B -- Verkade, Paul -- Woolfson, Derek N -- BB/G008833/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2013 May 3;340(6132):595-9. doi: 10.1126/science.1233936. Epub 2013 Apr 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Chemistry, Cantock's Close, University of Bristol, Bristol BS8 1TS, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23579496" target="_blank"〉PubMed〈/a〉
    Keywords: Circular Dichroism ; Microscopy, Electron, Scanning ; Models, Molecular ; Molecular Dynamics Simulation ; *Nanostructures ; Peptides/*chemistry ; Protein Conformation ; Protein Folding ; Protein Multimerization ; Protein Structure, Secondary ; Thermodynamics
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  • 22
    Publication Date: 2013-02-16
    Description: Intense femtosecond x-ray pulses produced at the Linac Coherent Light Source (LCLS) were used for simultaneous x-ray diffraction (XRD) and x-ray emission spectroscopy (XES) of microcrystals of photosystem II (PS II) at room temperature. This method probes the overall protein structure and the electronic structure of the Mn4CaO5 cluster in the oxygen-evolving complex of PS II. XRD data are presented from both the dark state (S1) and the first illuminated state (S2) of PS II. Our simultaneous XRD-XES study shows that the PS II crystals are intact during our measurements at the LCLS, not only with respect to the structure of PS II, but also with regard to the electronic structure of the highly radiation-sensitive Mn4CaO5 cluster, opening new directions for future dynamics studies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732582/" 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/PMC3732582/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kern, Jan -- Alonso-Mori, Roberto -- Tran, Rosalie -- Hattne, Johan -- Gildea, Richard J -- Echols, Nathaniel -- Glockner, Carina -- Hellmich, Julia -- Laksmono, Hartawan -- Sierra, Raymond G -- Lassalle-Kaiser, Benedikt -- Koroidov, Sergey -- Lampe, Alyssa -- Han, Guangye -- Gul, Sheraz -- Difiore, Dorte -- Milathianaki, Despina -- Fry, Alan R -- Miahnahri, Alan -- Schafer, Donald W -- Messerschmidt, Marc -- Seibert, M Marvin -- Koglin, Jason E -- Sokaras, Dimosthenis -- Weng, Tsu-Chien -- Sellberg, Jonas -- Latimer, Matthew J -- Grosse-Kunstleve, Ralf W -- Zwart, Petrus H -- White, William E -- Glatzel, Pieter -- Adams, Paul D -- Bogan, Michael J -- Williams, Garth J -- Boutet, Sebastien -- Messinger, Johannes -- Zouni, Athina -- Sauter, Nicholas K -- Yachandra, Vittal K -- Bergmann, Uwe -- Yano, Junko -- GM095887/GM/NIGMS NIH HHS/ -- GM102520/GM/NIGMS NIH HHS/ -- P01 GM063210/GM/NIGMS NIH HHS/ -- P41GM103393/GM/NIGMS NIH HHS/ -- R01 GM055302/GM/NIGMS NIH HHS/ -- R01 GM095887/GM/NIGMS NIH HHS/ -- R01 GM102520/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Apr 26;340(6131):491-5. doi: 10.1126/science.1234273. Epub 2013 Feb 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23413188" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray/methods ; Cyanobacteria/enzymology ; Electrons ; Light ; Manganese Compounds/*chemistry ; Oxidation-Reduction ; Oxides/*chemistry ; Photosystem II Protein Complex/*chemistry/radiation effects ; Protein Conformation ; Spectrometry, X-Ray Emission/methods ; Temperature ; Water/chemistry ; X-Ray Diffraction/methods
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  • 23
    Publication Date: 2013-12-21
    Description: X-ray crystallography of G protein-coupled receptors and other membrane proteins is hampered by difficulties associated with growing sufficiently large crystals that withstand radiation damage and yield high-resolution data at synchrotron sources. We used an x-ray free-electron laser (XFEL) with individual 50-femtosecond-duration x-ray pulses to minimize radiation damage and obtained a high-resolution room-temperature structure of a human serotonin receptor using sub-10-micrometer microcrystals grown in a membrane mimetic matrix known as lipidic cubic phase. Compared with the structure solved by using traditional microcrystallography from cryo-cooled crystals of about two orders of magnitude larger volume, the room-temperature XFEL structure displays a distinct distribution of thermal motions and conformations of residues that likely more accurately represent the receptor structure and dynamics in a cellular environment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902108/" 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/PMC3902108/" 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 -- Wacker, Daniel -- Gati, Cornelius -- Han, Gye Won -- James, Daniel -- Wang, Dingjie -- Nelson, Garrett -- Weierstall, Uwe -- Katritch, Vsevolod -- Barty, Anton -- Zatsepin, Nadia A -- Li, Dianfan -- Messerschmidt, Marc -- Boutet, Sebastien -- Williams, Garth J -- Koglin, Jason E -- Seibert, M Marvin -- Wang, Chong -- Shah, Syed T A -- Basu, Shibom -- Fromme, Raimund -- Kupitz, Christopher -- Rendek, Kimberley N -- Grotjohann, Ingo -- Fromme, Petra -- Kirian, Richard A -- Beyerlein, Kenneth R -- White, Thomas A -- Chapman, Henry N -- Caffrey, Martin -- Spence, John C H -- Stevens, Raymond C -- Cherezov, Vadim -- P50 GM073197/GM/NIGMS NIH HHS/ -- P50 GM073210/GM/NIGMS NIH HHS/ -- R01 GM095583/GM/NIGMS NIH HHS/ -- U54 GM094599/GM/NIGMS NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Dec 20;342(6165):1521-4. doi: 10.1126/science.1244142.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational 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/24357322" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray/*instrumentation/*methods ; Humans ; Lasers ; Protein Conformation ; Receptor, Serotonin, 5-HT2B/chemistry/radiation effects ; Receptors, G-Protein-Coupled/*chemistry/radiation effects ; Time Factors
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  • 24
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-01-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Forrest, Lucy R -- New York, N.Y. -- Science. 2013 Jan 25;339(6118):399-401. doi: 10.1126/science.1228465.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Computational Structural Biology Group, Max Planck Institute of Biophysics, Max-von-Laue-Strasse 3, 60438 Frankfurt am Main, Germany. lucy.forrest@biophys.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23349276" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Biological Transport ; Cell Membrane/chemistry ; Ion Channels/chemistry/metabolism ; Membrane Transport Proteins/*chemistry/metabolism ; Models, Molecular ; Protein Conformation ; Protein Folding ; Protein Multimerization ; Protein Structure, Secondary
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  • 25
    Publication Date: 2013-08-24
    Description: Many studies have implicated a role for conformational motions during the catalytic cycle, acting to optimize the binding pocket or facilitate product release, but a more intimate role in the chemical reaction has not been described. We address this by monitoring active-site loop motion in two protein tyrosine phosphatases (PTPs) using nuclear magnetic resonance spectroscopy. The PTPs, YopH and PTP1B, have very different catalytic rates; however, we find in both that the active-site loop closes to its catalytically competent position at rates that mirror the phosphotyrosine cleavage kinetics. This loop contains the catalytic acid, suggesting that loop closure occurs concomitantly with the protonation of the leaving group tyrosine and explains the different kinetics of two otherwise chemically and mechanistically indistinguishable enzymes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078984/" 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/PMC4078984/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whittier, Sean K -- Hengge, Alvan C -- Loria, J Patrick -- GM47297/GM/NIGMS NIH HHS/ -- T32 GM008283/GM/NIGMS NIH HHS/ -- T32GM008283/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Aug 23;341(6148):899-903. doi: 10.1126/science.1241735.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Avenue, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23970698" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Outer Membrane Proteins/*chemistry ; Catalysis ; Catalytic Domain ; Humans ; Motion ; Nuclear Magnetic Resonance, Biomolecular ; Phosphates/*chemistry ; Protein Conformation ; Protein Tyrosine Phosphatase, Non-Receptor Type 1/*chemistry ; Protein Tyrosine Phosphatases/*chemistry ; Vanadates/chemistry
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  • 26
    Publication Date: 2013-03-23
    Description: Drugs active at G protein-coupled receptors (GPCRs) can differentially modulate either canonical or noncanonical signaling pathways via a phenomenon known as functional selectivity or biased signaling. We report biochemical studies showing that the hallucinogen lysergic acid diethylamide, its precursor ergotamine (ERG), and related ergolines display strong functional selectivity for beta-arrestin signaling at the 5-HT2B 5-hydroxytryptamine (5-HT) receptor, whereas they are relatively unbiased at the 5-HT1B receptor. To investigate the structural basis for biased signaling, we determined the crystal structure of the human 5-HT2B receptor bound to ERG and compared it with the 5-HT1B/ERG structure. Given the relatively poor understanding of GPCR structure and function to date, insight into different GPCR signaling pathways is important to better understand both adverse and favorable therapeutic activities.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644390/" 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/PMC3644390/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wacker, Daniel -- Wang, Chong -- Katritch, Vsevolod -- Han, Gye Won -- Huang, Xi-Ping -- Vardy, Eyal -- McCorvy, John D -- Jiang, Yi -- Chu, Meihua -- Siu, Fai Yiu -- Liu, Wei -- Xu, H Eric -- Cherezov, Vadim -- Roth, Bryan L -- Stevens, Raymond C -- P50 GM073197/GM/NIGMS NIH HHS/ -- R01 DK071662/DK/NIDDK NIH HHS/ -- R01 MH061887/MH/NIMH NIH HHS/ -- R01 MH61887/MH/NIMH NIH HHS/ -- U19 MH082441/MH/NIMH NIH HHS/ -- U19 MH82441/MH/NIMH 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. 2013 May 3;340(6132):615-9. doi: 10.1126/science.1232808. Epub 2013 Mar 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational 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/23519215" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Arrestin/metabolism ; Arrestins/metabolism ; Binding Sites ; Crystallography, X-Ray ; Ergolines/chemistry/metabolism ; Ergotamine/chemistry/*metabolism ; HEK293 Cells ; Humans ; Ligands ; Lysergic Acid Diethylamide/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Structure, Secondary ; Receptor, Serotonin, 5-HT1B/chemistry/*metabolism ; Receptor, Serotonin, 5-HT2B/*chemistry/*metabolism ; Receptors, Serotonin/chemistry/metabolism ; Signal Transduction
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  • 27
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-09-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2013 Sep 13;341(6151):1168-71. doi: 10.1126/science.341.6151.1168.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24030996" target="_blank"〉PubMed〈/a〉
    Keywords: *AIDS Vaccines ; Acquired Immunodeficiency Syndrome/*immunology/*prevention & control ; HIV Antibodies/*chemistry/*immunology ; HIV Envelope Protein gp120/chemistry/immunology ; HIV Envelope Protein gp41/chemistry/immunology ; Humans ; Models, Chemical ; Protein Conformation
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  • 28
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-08-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2013 Aug 2;341(6145):443-4. doi: 10.1126/science.341.6145.443.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23908196" target="_blank"〉PubMed〈/a〉
    Keywords: *Artifacts ; Cryoelectron Microscopy/*methods ; HIV/immunology/*ultrastructure ; HIV Envelope Protein gp120/*chemistry/immunology ; HIV Envelope Protein gp41/*chemistry/immunology ; Humans ; Immune System/virology ; Protein Conformation ; Protein Multimerization
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  • 29
    Publication Date: 2013-02-23
    Description: Influenza antiviral agents play important roles in modulating disease severity and in controlling pandemics while vaccines are prepared, but the development of resistance to agents like the commonly used neuraminidase inhibitor oseltamivir may limit their future utility. We report here on a new class of specific, mechanism-based anti-influenza drugs that function through the formation of a stabilized covalent intermediate in the influenza neuraminidase enzyme, and we confirm this mode of action with structural and mechanistic studies. These compounds function in cell-based assays and in animal models, with efficacies comparable to that of the neuraminidase inhibitor zanamivir and with broad-spectrum activity against drug-resistant strains in vitro. The similarity of their structure to that of the natural substrate and their mechanism-based design make these attractive antiviral candidates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jin-Hyo -- Resende, Ricardo -- Wennekes, Tom -- Chen, Hong-Ming -- Bance, Nicole -- Buchini, Sabrina -- Watts, Andrew G -- Pilling, Pat -- Streltsov, Victor A -- Petric, Martin -- Liggins, Richard -- Barrett, Susan -- McKimm-Breschkin, Jennifer L -- Niikura, Masahiro -- Withers, Stephen G -- G0600514/Medical Research Council/United Kingdom -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2013 Apr 5;340(6128):71-5. doi: 10.1126/science.1232552. Epub 2013 Feb 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23429702" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antiviral Agents/*chemistry/pharmacology ; Crystallography, X-Ray ; Dogs ; Enzyme Inhibitors/*chemistry/pharmacology ; Humans ; Madin Darby Canine Kidney Cells ; Neuraminidase/*antagonists & inhibitors/chemistry ; Orthomyxoviridae/*drug effects/enzymology ; Oseltamivir/chemistry/pharmacology ; Protein Conformation ; Sialic Acids/*chemistry/pharmacology ; Structure-Activity Relationship ; Zanamivir/chemistry/pharmacology
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  • 30
    Publication Date: 2013-05-11
    Description: Serum characterization and antibody isolation are transforming our understanding of the humoral immune response to viral infection. Here, we show that epitope specificities of HIV-1-neutralizing antibodies in serum can be elucidated from the serum pattern of neutralization against a diverse panel of HIV-1 isolates. We determined "neutralization fingerprints" for 30 neutralizing antibodies on a panel of 34 diverse HIV-1 strains and showed that similarity in neutralization fingerprint correlated with similarity in epitope. We used these fingerprints to delineate specificities of polyclonal sera from 24 HIV-1-infected donors and a chimeric siman-human immunodeficiency virus-infected macaque. Delineated specificities matched published specificities and were further confirmed by antibody isolation for two sera. Patterns of virus-isolate neutralization can thus afford a detailed epitope-specific understanding of neutralizing-antibody responses to viral infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Georgiev, Ivelin S -- Doria-Rose, Nicole A -- Zhou, Tongqing -- Kwon, Young Do -- Staupe, Ryan P -- Moquin, Stephanie -- Chuang, Gwo-Yu -- Louder, Mark K -- Schmidt, Stephen D -- Altae-Tran, Han R -- Bailer, Robert T -- McKee, Krisha -- Nason, Martha -- O'Dell, Sijy -- Ofek, Gilad -- Pancera, Marie -- Srivatsan, Sanjay -- Shapiro, Lawrence -- Connors, Mark -- Migueles, Stephen A -- Morris, Lynn -- Nishimura, Yoshiaki -- Martin, Malcolm A -- Mascola, John R -- Kwong, Peter D -- U19 AI51794/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 May 10;340(6133):751-6. doi: 10.1126/science.1233989.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23661761" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Neutralizing/blood/*immunology ; Epitope Mapping ; HIV Antibodies/blood/*immunology ; HIV Infections/blood/*immunology ; HIV-1/*immunology/isolation & purification ; Humans ; Immunodominant Epitopes/chemistry/immunology ; Macaca ; Neutralization Tests ; Protein Conformation ; Serum/immunology
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  • 31
    Publication Date: 2013-04-27
    Description: The prefusion state of respiratory syncytial virus (RSV) fusion (F) glycoprotein is the target of most RSV-neutralizing activity in human sera, but its metastability has hindered characterization. To overcome this obstacle, we identified prefusion-specific antibodies that were substantially more potent than the prophylactic antibody palivizumab. The cocrystal structure for one of these antibodies, D25, in complex with the F glycoprotein revealed D25 to lock F in its prefusion state by binding to a quaternary epitope at the trimer apex. Electron microscopy showed that two other antibodies, AM22 and 5C4, also bound to the newly identified site of vulnerability, which we named antigenic site O. These studies should enable design of improved vaccine antigens and define new targets for passive prevention of RSV-induced disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459498/" 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/PMC4459498/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McLellan, Jason S -- Chen, Man -- Leung, Sherman -- Graepel, Kevin W -- Du, Xiulian -- Yang, Yongping -- Zhou, Tongqing -- Baxa, Ulrich -- Yasuda, Etsuko -- Beaumont, Tim -- Kumar, Azad -- Modjarrad, Kayvon -- Zheng, Zizheng -- Zhao, Min -- Xia, Ningshao -- Kwong, Peter D -- Graham, Barney S -- ZIA AI005024-11/Intramural NIH HHS/ -- ZIA AI005061-10/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 May 31;340(6136):1113-7. doi: 10.1126/science.1234914. Epub 2013 Apr 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. mclellanja@niaid.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23618766" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antibodies, Monoclonal, Humanized/immunology ; Antibodies, Neutralizing/chemistry/*immunology ; Crystallography, X-Ray ; Female ; Glycoproteins/chemistry/*immunology ; HEK293 Cells ; Humans ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Neutralization Tests ; Palivizumab ; Protein Conformation ; Protein Multimerization ; Respiratory Syncytial Virus Vaccines/chemistry/*immunology ; Respiratory Syncytial Viruses/*immunology/physiology ; Viral Fusion Proteins/chemistry/*immunology ; Virus Internalization
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  • 32
    Publication Date: 2013-09-14
    Description: The CCR5 chemokine receptor acts as a co-receptor for HIV-1 viral entry. Here we report the 2.7 angstrom-resolution crystal structure of human CCR5 bound to the marketed HIV drug maraviroc. The structure reveals a ligand-binding site that is distinct from the proposed major recognition sites for chemokines and the viral glycoprotein gp120, providing insights into the mechanism of allosteric inhibition of chemokine signaling and viral entry. A comparison between CCR5 and CXCR4 crystal structures, along with models of co-receptor-gp120-V3 complexes, suggests that different charge distributions and steric hindrances caused by residue substitutions may be major determinants of HIV-1 co-receptor selectivity. These high-resolution insights into CCR5 can enable structure-based drug discovery for the treatment of HIV-1 infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819204/" 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/PMC3819204/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tan, Qiuxiang -- Zhu, Ya -- Li, Jian -- Chen, Zhuxi -- Han, Gye Won -- Kufareva, Irina -- Li, Tingting -- Ma, Limin -- Fenalti, Gustavo -- Li, Jing -- Zhang, Wenru -- Xie, Xin -- Yang, Huaiyu -- Jiang, Hualiang -- Cherezov, Vadim -- Liu, Hong -- Stevens, Raymond C -- Zhao, Qiang -- Wu, Beili -- R01 AI100604/AI/NIAID NIH HHS/ -- R01 GM071872/GM/NIGMS NIH HHS/ -- U01 GM094612/GM/NIGMS NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Sep 20;341(6152):1387-90. doi: 10.1126/science.1241475. Epub 2013 Sep 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai, China 201203.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24030490" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cyclohexanes/*chemistry/pharmacology ; HIV Envelope Protein gp120/metabolism ; HIV Fusion Inhibitors/*chemistry/pharmacology ; HIV-1/*drug effects/physiology ; Humans ; Ligands ; Protein Conformation ; Receptors, CCR5/*chemistry/metabolism ; Receptors, CXCR4/chemistry ; Triazoles/*chemistry/pharmacology ; Virus Internalization/*drug effects
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  • 33
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-07-03
    Description: Protein synthesis by the ribosome requires the translocation of transfer RNAs and messenger RNA by one codon after each peptide bond is formed, a reaction that requires ribosomal subunit rotation and is catalyzed by the guanosine triphosphatase (GTPase) elongation factor G (EF-G). We determined 3 angstrom resolution x-ray crystal structures of EF-G complexed with a nonhydrolyzable guanosine 5'-triphosphate (GTP) analog and bound to the Escherichia coli ribosome in different states of ribosomal subunit rotation. The structures reveal that EF-G binding to the ribosome stabilizes switch regions in the GTPase active site, resulting in a compact EF-G conformation that favors an intermediate state of ribosomal subunit rotation. These structures suggest that EF-G controls the translocation reaction by cycles of conformational rigidity and relaxation before and after GTP hydrolysis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274944/" 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/PMC4274944/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pulk, Arto -- Cate, Jamie H D -- R01 GM065050/GM/NIGMS NIH HHS/ -- R01 GM105404/GM/NIGMS NIH HHS/ -- R01-GM65050/GM/NIGMS NIH HHS/ -- R01GM105404/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jun 28;340(6140):1235970. doi: 10.1126/science.1235970.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23812721" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Escherichia coli/*enzymology ; Guanosine Triphosphate/*chemistry ; Hydrolysis ; Models, Biological ; Peptide Elongation Factor G/*chemistry ; *Protein Biosynthesis ; Protein Conformation ; Protein Structure, Tertiary ; RNA, Messenger/chemistry ; RNA, Transfer/chemistry ; Ribosome Subunits, Large, Bacterial/*chemistry ; Rotation
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  • 34
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-01-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bowie, James U -- R01GM063919/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jan 25;339(6118):398-9. doi: 10.1126/science.1228655.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, UCLA-DOE Institute of Genomics and Proteomics, University of California, Los Angeles, Los Angeles, CA 90095, USA. bowie@mbi.ucla.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23349275" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Membrane/*chemistry ; Hydrogen Bonding ; Lipid Bilayers/chemistry ; Membrane Proteins/*chemistry ; Models, Molecular ; Protein Conformation ; *Protein Folding ; Protein Structure, Secondary ; Protein Subunits/chemistry
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  • 35
    Publication Date: 2013-05-11
    Description: Mutations in the PARK2 (parkin) gene are responsible for an autosomal recessive form of Parkinson's disease. The parkin protein is a RING-in-between-RING E3 ubiquitin ligase that exhibits low basal activity. We describe the crystal structure of full-length rat parkin. The structure shows parkin in an autoinhibited state and provides insight into how it is activated. RING0 occludes the ubiquitin acceptor site Cys(431) in RING2, whereas a repressor element of parkin binds RING1 and blocks its E2-binding site. Mutations that disrupted these inhibitory interactions activated parkin both in vitro and in cells. Parkin is neuroprotective, and these findings may provide a structural and mechanistic framework for enhancing parkin activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trempe, Jean-Francois -- Sauve, Veronique -- Grenier, Karl -- Seirafi, Marjan -- Tang, Matthew Y -- Menade, Marie -- Al-Abdul-Wahid, Sameer -- Krett, Jonathan -- Wong, Kathy -- Kozlov, Guennadi -- Nagar, Bhushan -- Fon, Edward A -- Gehring, Kalle -- MOP-14219/Canadian Institutes of Health Research/Canada -- MOP-62714/Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2013 Jun 21;340(6139):1451-5. doi: 10.1126/science.1237908. Epub 2013 May 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23661642" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Catalytic Domain ; Crystallography, X-Ray ; Enzyme Activation ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Parkinson Disease ; Parkinsonian Disorders ; Protein Binding ; Protein Conformation ; Protein Folding ; Protein Structure, Tertiary ; Rats ; Ubiquitin-Protein Ligases/*chemistry/genetics/*metabolism ; Ubiquitination ; Zinc Fingers
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  • 36
    Publication Date: 2013-05-04
    Description: Recent studies have identified several mutations in the hemagglutinin (HA) protein that allow the highly pathogenic avian H5N1 influenza A virus to transmit between mammals by airborne route. Here, we determined the complex structures of wild-type and mutant HAs derived from an Indonesia H5N1 virus bound to either avian or human receptor sialic acid analogs. A cis/trans conformational change in the glycosidic linkage of the receptor analog was observed, which explains how the H5N1 virus alters its receptor-binding preference. Furthermore, the mutant HA possessed low affinities for both avian and human receptors. Our findings provide a structural and biophysical basis for the H5N1 adaptation to acquire human, but maintain avian, receptor-binding properties.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Wei -- Shi, Yi -- Lu, Xishan -- Shu, Yuelong -- Qi, Jianxun -- Gao, George F -- New York, N.Y. -- Science. 2013 Jun 21;340(6139):1463-7. doi: 10.1126/science.1236787. Epub 2013 May 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23641058" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Birds ; Carbohydrate Conformation ; Crystallography, X-Ray ; Hemagglutinin Glycoproteins, Influenza Virus/*chemistry/genetics/*metabolism ; Humans ; Influenza A Virus, H5N1 Subtype ; Models, Molecular ; Mutant Proteins/chemistry/metabolism ; Mutation ; Oligosaccharides/chemistry/metabolism ; Protein Binding ; Protein Conformation ; Protein Stability ; Receptors, Cell Surface/chemistry/*metabolism ; Receptors, Virus/chemistry/*metabolism ; Recombinant Proteins/chemistry/metabolism
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  • 37
    Publication Date: 2013-08-31
    Description: Tissues can be soft like fat, which bears little stress, or stiff like bone, which sustains high stress, but whether there is a systematic relationship between tissue mechanics and differentiation is unknown. Here, proteomics analyses revealed that levels of the nucleoskeletal protein lamin-A scaled with tissue elasticity, E, as did levels of collagens in the extracellular matrix that determine E. Stem cell differentiation into fat on soft matrix was enhanced by low lamin-A levels, whereas differentiation into bone on stiff matrix was enhanced by high lamin-A levels. Matrix stiffness directly influenced lamin-A protein levels, and, although lamin-A transcription was regulated by the vitamin A/retinoic acid (RA) pathway with broad roles in development, nuclear entry of RA receptors was modulated by lamin-A protein. Tissue stiffness and stress thus increase lamin-A levels, which stabilize the nucleus while also contributing to lineage determination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976548/" 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/PMC3976548/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Swift, Joe -- Ivanovska, Irena L -- Buxboim, Amnon -- Harada, Takamasa -- Dingal, P C Dave P -- Pinter, Joel -- Pajerowski, J David -- Spinler, Kyle R -- Shin, Jae-Won -- Tewari, Manorama -- Rehfeldt, Florian -- Speicher, David W -- Discher, Dennis E -- 8UL1TR000003/TR/NCATS NIH HHS/ -- CA010815/CA/NCI NIH HHS/ -- HL038794/HL/NHLBI NIH HHS/ -- P01DK032094/DK/NIDDK NIH HHS/ -- P30-DK090969/DK/NIDDK NIH HHS/ -- R01 EB007049/EB/NIBIB NIH HHS/ -- R01 HL062352/HL/NHLBI NIH HHS/ -- R01EB007049/EB/NIBIB NIH HHS/ -- R01HL062352/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2013 Aug 30;341(6149):1240104. doi: 10.1126/science.1240104.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular and Cell Biophysics Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23990565" target="_blank"〉PubMed〈/a〉
    Keywords: Adipogenesis ; Animals ; *Cell Differentiation ; Collagen/analysis/chemistry/metabolism ; *Elasticity ; Extracellular Matrix/chemistry/metabolism ; Gene Expression Regulation, Developmental ; Humans ; Lamin Type A/chemistry/genetics/*metabolism ; Mesenchymal Stromal Cells/*cytology ; Mice ; Models, Biological ; Nuclear Lamina/metabolism ; *Osteogenesis/genetics ; Protein Conformation ; Proteome ; *Stress, Mechanical ; Transcription, Genetic ; Tretinoin/metabolism ; Vitamin A/metabolism
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  • 38
    Publication Date: 2013-07-03
    Description: Translocation of messenger and transfer RNA (mRNA and tRNA) through the ribosome is a crucial step in protein synthesis, whose mechanism is not yet understood. The crystal structures of three Thermus ribosome-tRNA-mRNA-EF-G complexes trapped with beta,gamma-imidoguanosine 5'-triphosphate (GDPNP) or fusidic acid reveal conformational changes occurring during intermediate states of translocation, including large-scale rotation of the 30S subunit head and body. In all complexes, the tRNA acceptor ends occupy the 50S subunit E site, while their anticodon stem loops move with the head of the 30S subunit to positions between the P and E sites, forming chimeric intermediate states. Two universally conserved bases of 16S ribosomal RNA that intercalate between bases of the mRNA may act as "pawls" of a translocational ratchet. These findings provide new insights into the molecular mechanism of ribosomal translocation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979973/" 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/PMC3979973/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Jie -- Lancaster, Laura -- Donohue, John Paul -- Noller, Harry F -- GM-105404/GM/NIGMS NIH HHS/ -- GM-17129/GM/NIGMS NIH HHS/ -- GM-59140/GM/NIGMS NIH HHS/ -- P41-GM-103393/GM/NIGMS NIH HHS/ -- R01 GM017129/GM/NIGMS NIH HHS/ -- R01 GM059140/GM/NIGMS NIH HHS/ -- R01 GM105404/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jun 28;340(6140):1236086. doi: 10.1126/science.1236086.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Molecular Biology of RNA and Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA 95064, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23812722" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Fusidic Acid/chemistry ; Guanosine Triphosphate/analogs & derivatives/chemistry ; Peptide Elongation Factor G/*chemistry ; *Protein Biosynthesis ; Protein Conformation ; RNA, Messenger/chemistry ; RNA, Transfer/chemistry ; Ribosome Subunits, Large, Bacterial/*chemistry ; Thermus thermophilus/*enzymology
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  • 39
    Publication Date: 1996-06-07
    Description: Molecular chaperones in the eukaryotic cytosol were shown to interact differently with chemically denatured proteins and their newly translated counterparts. During refolding from denaturant, actin partitioned freely between 70-kilodalton heat shock protein, the bulk cytosol, and the chaperonin TCP1-ring complex. In contrast, during cell-free translation, the chaperones were recruited to the elongating polypeptide and protected it from exposure to the bulk cytosol during folding. Posttranslational cycling between chaperone-bound and free states was observed with subunits of oligomeric proteins and with aberrant polypeptides; this cycling allowed the subunits to assemble and the aberrant polypeptides to be degraded. Thus, folding, oligomerization, and degradation are linked hierarchically to ensure the correct fate of newly synthesized polypeptides.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Frydman, J -- Hartl, F U -- New York, N.Y. -- Science. 1996 Jun 7;272(5267):1497-502.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8633246" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*chemistry/genetics/metabolism ; Adenosine Triphosphate/metabolism ; Cell Extracts ; Chaperonin 60/chemistry/metabolism ; Chaperonin Containing TCP-1 ; Chaperonins/chemistry/metabolism ; HSP70 Heat-Shock Proteins/chemistry/metabolism ; Luciferases/*chemistry/genetics/metabolism ; Molecular Chaperones/chemistry/*metabolism ; Peptides/chemistry/metabolism ; *Protein Biosynthesis ; Protein Conformation ; Protein Denaturation ; *Protein Folding ; Reticulocytes ; Ribosomes/metabolism
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  • 40
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-12-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perros, M -- Steitz, T A -- New York, N.Y. -- Science. 1996 Dec 13;274(5294):1929-30; author reply 1931-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8984647" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Crystallography, X-Ray ; Cyclic AMP Receptor Protein/*metabolism ; DNA, Bacterial/chemistry/*metabolism ; Escherichia coli/genetics ; *Lac Operon ; Molecular Sequence Data ; *Nucleic Acid Conformation ; Operator Regions, Genetic ; *Promoter Regions, Genetic ; Protein Binding ; Protein Conformation ; Repressor Proteins/chemistry/*metabolism
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  • 41
    Publication Date: 1996-04-26
    Description: Electrostatic interactions between charges on ligands and charges on proteins that are remote from the binding interface can influence the free energy of binding (delta Gb). The binding affinities between charged ligands and the members of a charge ladder of bovine carbonic anhydrase (CAII) constructed by random acetylation of the amino groups on its surface were measured by affinity capillary electrophoresis (ACE). The values of delta Gb derived from this analysis correlated approximately linearly with the charge. Opposite charges on the ligand and the members of the charge ladder of CAII were stabilizing; like charges were destabilizing. The combination of ACE and protein charge ladders provides a tool for quantitatively examining the contributions of electrostatics to free energies of molecular recognition in biology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gao, J -- Mammen, M -- Whitesides, G M -- GM51559/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Apr 26;272(5261):535-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8614800" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Animals ; Binding Sites ; Carbonic Anhydrases/*chemistry/*metabolism ; Cattle ; Electrochemistry ; Electrophoresis, Capillary ; Ligands ; Models, Chemical ; Molecular Weight ; Protein Conformation ; Sulfonamides/metabolism ; Thermodynamics
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  • 42
    Publication Date: 1996-07-12
    Description: The three-dimensional structure of the amino-terminal core domain (residues 1 through 151) of the human immunodeficiency virus-type 1 (HIV-1) capsid protein has been solved by multidimensional heteronuclear magnetic resonance spectroscopy. The structure is unlike those of previously characterized viral coat proteins and is composed of seven alpha helices, two beta hairpins, and an exposed partially ordered loop. The domain is shaped like an arrowhead, with the beta hairpins and loop exposed at the trailing edge and the carboxyl-terminal helix projecting from the tip. The proline residue Pro1 forms a salt bridge with a conserved, buried aspartate residue (Asp51), which suggests that the amino terminus of the protein rearranges upon proteolytic maturation. The binding site for cyclophilin A, a cellular rotamase that is packaged into the HIV-1 virion, is located on the exposed loop and encompasses the essential proline residue Pro90. In the free monomeric domain, Pro90 adopts kinetically trapped cis and trans conformations, raising the possibility that cyclophilin A catalyzes interconversion of the cis- and trans-Pro90 loop structures.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gitti, R K -- Lee, B M -- Walker, J -- Summers, M F -- Yoo, S -- Sundquist, W I -- AI30917/AI/NIAID NIH HHS/ -- CA 42014/CA/NCI NIH HHS/ -- GM 42561/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Jul 12;273(5272):231-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Maryland Baltimore County, Baltimore, MD 21228, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8662505" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Isomerases/metabolism ; Amino Acid Sequence ; Aspartic Acid/chemistry ; Binding Sites ; Capsid/*chemistry/metabolism ; Carrier Proteins/metabolism ; HIV Core Protein p24/*chemistry/metabolism ; HIV-1/*chemistry ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Molecular Sequence Data ; Peptidylprolyl Isomerase ; Proline/chemistry ; Protein Conformation ; Protein Processing, Post-Translational ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Virion/chemistry
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  • 43
    Publication Date: 1996-12-20
    Description: Enoyl reductase (ENR), an enzyme involved in fatty acid biosynthesis, is the target for antibacterial diazaborines and the front-line antituberculosis drug isoniazid. Analysis of the structures of complexes of Escherichia coli ENR with nicotinamide adenine dinucleotide and either thienodiazaborine or benzodiazaborine revealed the formation of a covalent bond between the 2' hydroxyl of the nicotinamide ribose and a boron atom in the drugs to generate a tight, noncovalently bound bisubstrate analog. This analysis has implications for the structure-based design of inhibitors of ENR, and similarities to other oxidoreductases suggest that mimicking this molecular linkage may have generic applications in other areas of medicinal chemistry.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baldock, C -- Rafferty, J B -- Sedelnikova, S E -- Baker, P J -- Stuitje, A R -- Slabas, A R -- Hawkes, T R -- Rice, D W -- New York, N.Y. -- Science. 1996 Dec 20;274(5295):2107-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, UK. D.Rice@sheffield.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8953047" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-Bacterial Agents/*metabolism/pharmacology ; Binding Sites ; Boron Compounds/*metabolism/pharmacology ; Crystallography, X-Ray ; Drug Design ; Drug Resistance, Microbial ; Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) ; Enzyme Inhibitors/*metabolism/pharmacology ; Escherichia coli/enzymology ; Escherichia coli Proteins ; Fatty Acid Synthase, Type II ; Fatty Acid Synthases/antagonists & inhibitors/*chemistry/metabolism ; Hydrogen Bonding ; Models, Molecular ; NAD/*metabolism ; Oxidoreductases/antagonists & inhibitors/*chemistry/metabolism ; Protein Conformation ; Protein Structure, Secondary
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  • 44
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-12-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Engelman, D M -- New York, N.Y. -- Science. 1996 Dec 13;274(5294):1850-1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics, Yale University, New Haven, CT 06520, USA. don@paradigm.csb.yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8984645" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Toxins/*chemistry/metabolism ; Colicins/chemistry ; Hemolysin Proteins/*chemistry/metabolism ; Hydrogen Bonding ; Lipid Bilayers/*chemistry/metabolism ; Membrane Proteins/*chemistry/metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary
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  • 45
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-05-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jacobson, R H -- Tjian, R -- New York, N.Y. -- Science. 1996 May 10;272(5263):827-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of California, Berkeley 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8629011" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Crystallography, X-Ray ; DNA/*chemistry/metabolism ; DNA-Binding Proteins/*chemistry/metabolism ; Humans ; Models, Molecular ; Nucleic Acid Conformation ; Protein Conformation ; Protein Structure, Secondary ; TATA Box ; TATA-Box Binding Protein ; Transcription Factor TFIIA ; Transcription Factor TFIID ; Transcription Factors/*chemistry/genetics/*metabolism ; *Transcription, Genetic
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  • 46
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-05-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, I A -- New York, N.Y. -- Science. 1996 May 17;272(5264):973-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, 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/8638141" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen Presentation ; Antigens/chemistry/*metabolism ; Antigens, Differentiation, B-Lymphocyte/chemistry/*metabolism ; HLA-DR1 Antigen/chemistry/metabolism ; Histocompatibility Antigens Class II/chemistry/immunology/*metabolism ; Humans ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Mice ; Models, Molecular ; Protein Conformation
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 47
    Publication Date: 1996-01-05
    Description: The molecular origin of the exceptional mechanical properties of spider silk is unclear. This paper presents solid-state 2H nuclear magnetic resonance data from unoriented, oriented, and supercontracted fibers, indicating that the crystalline fraction of dragline silk consists of two types of alanine-rich regions, one that is highly oriented and one that is poorly oriented and less densely packed. A new model for the molecular-level structure of individual silk molecules and their arrangement in the fibers is proposed. These data suggest that it will be necessary to control the secondary structure of individual polymer molecules in order to obtain optimum properties in bio-inspired polymers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simmons, A H -- Michal, C A -- Jelinski, L W -- New York, N.Y. -- Science. 1996 Jan 5;271(5245):84-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Advanced Technology in Biotechnology, Cornell University, Ithaca, NY 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8539605" target="_blank"〉PubMed〈/a〉
    Keywords: Alanine/analysis ; Algorithms ; Amino Acid Sequence ; Animals ; Crystallization ; Crystallography, X-Ray ; *Fibroins ; Glycine/analysis ; *Insect Proteins ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Molecular Sequence Data ; Peptides/analysis ; Protein Conformation ; Protein Structure, Secondary ; Proteins/*chemistry ; Silk ; Spiders/*chemistry
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  • 48
    Publication Date: 1996-12-06
    Description: Molecular chaperones are essential proteins that participate in the regulation of steroid receptors in eukaryotes. The steroid aporeceptor complex contains the molecular chaperones Hsp90 and Hsp70, p48, the cyclophilin Cyp-40, and the associated proteins p23 and p60. In vitro folding assays showed that Cyp-40 and p23 functioned as molecular chaperones in a manner similar to that of Hsp90 or Hsp70. Although neither Cyp-40 nor p23 could completely refold an unfolded substrate, both proteins interacted with the substrate to maintain a nonnative folding-competent intermediate. Thus, the steroid aporeceptor complexes have multiple chaperone components that maintain substrates in an intermediate folded state.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Freeman, B C -- Toft, D O -- Morimoto, R I -- GM38109/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Dec 6;274(5293):1718-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Molecular Biology and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, 2153 North Campus Drive, Evanston, IL 60208, USA. r-morimoto@nwu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8939864" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Isomerases/metabolism/*physiology ; Carrier Proteins/metabolism/*physiology ; *Cyclophilins ; HSC70 Heat-Shock Proteins ; HSP40 Heat-Shock Proteins ; HSP70 Heat-Shock Proteins/metabolism ; Heat-Shock Proteins/metabolism ; Hot Temperature ; Molecular Chaperones/metabolism/*physiology ; *Peptidylprolyl Isomerase ; Phosphoproteins/metabolism/*physiology ; Protein Conformation ; Protein Denaturation ; *Protein Folding ; Solubility ; beta-Galactosidase/chemistry
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  • 49
    Publication Date: 1996-02-23
    Description: Transmembrane signaling by bacterial chemotaxis receptors appears to require a conformational change within a receptor dimer. Dimers were engineered of the cytoplasmic domain of the Escherichia coli aspartate receptor that stimulated the kinase CheA in vitro. The folding free energy of the leucine-zipper dimerization domain was harnessed to twist the dimer interface of the receptor, which markedly affected the extent of CheA activation. Response to this twist was attenuated by modification of receptor regulatory sites, in the same manner as adaptation resets sensitivity to ligand in vivo. These results suggest that the normal allosteric activation of the chemotaxis receptor has been mimicked in a system that lacks both ligand-binding and transmembrane domains. The most stimulatory receptor dimer formed a species of tetrameric size.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cochran, A G -- Kim, P S -- T32 AI07348-07/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1996 Feb 23;271(5252):1113-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8599087" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/chemistry/*metabolism ; Chemoreceptor Cells ; Chemotaxis ; Cytoplasm/metabolism ; Enzyme Activation ; Escherichia coli/*metabolism ; *Escherichia coli Proteins ; Leucine Zippers ; Ligands ; Membrane Proteins/chemistry/*metabolism ; Methylation ; Molecular Sequence Data ; Phosphorylation ; Protein Conformation ; Protein Kinases/metabolism ; Protein Structure, Secondary ; Receptors, Amino Acid/chemistry/*metabolism ; *Receptors, Cell Surface ; Recombinant Fusion Proteins/chemistry/metabolism ; *Signal Transduction
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  • 50
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-10-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, J -- New York, N.Y. -- Science. 1996 Oct 25;274(5287):502.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8928003" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, CD4/*metabolism ; Cell Membrane/metabolism/virology ; HIV/*metabolism ; HIV Envelope Protein gp120/metabolism ; HIV Envelope Protein gp41/metabolism ; Humans ; Membrane Proteins/*metabolism ; Protein Conformation ; Receptors, CCR5 ; Receptors, CXCR4 ; Receptors, Cytokine/metabolism ; Receptors, HIV/*metabolism ; T-Lymphocytes/*virology
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  • 51
    Publication Date: 1996-03-08
    Description: Glutamic acid-203 of the alpha subunit of transducin (alphaT) resides within a domain that undergoes a guanosine triphosphate (GTP)-induced conformational change that is essential for effector recognition. Changing the glutamic acid to an alanine in bovine alpha(T) yielded an alpha subunit (alpha(T)E203A) that was fully dependent on rhodopsin for GTP-guanosine diphosphate (GDP) exchange and showed GTP hydrolytic activity similar to that measured for wild-type alpha(T). However, unlike the wild-type protein, the GDP-bound form of alpha(T)E203A was constitutively active toward the effector of transducin, the cyclic guanosine monophosphate phosphodiesterase. Thus, the alpha(T)E203A mutant represents a short-circuited protein switch that no longer requires GTP for the activation of the effector target phosphodiesterase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mittal, R -- Erickson, J W -- Cerione, R A -- New York, N.Y. -- Science. 1996 Mar 8;271(5254):1413-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Cornell University, Ithaca, NY 14853-6401, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8596913" target="_blank"〉PubMed〈/a〉
    Keywords: 3',5'-Cyclic-GMP Phosphodiesterases/*metabolism ; Adenosine Diphosphate Ribose/metabolism ; Alanine/chemistry ; Animals ; Base Sequence ; Cattle ; Enzyme Activation ; Glutamic Acid/chemistry ; Guanosine 5'-O-(3-Thiotriphosphate)/metabolism ; Guanosine Diphosphate/metabolism ; Guanosine Triphosphate/*metabolism ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Recombinant Fusion Proteins ; Rhodopsin/metabolism ; Transducin/chemistry/genetics/*metabolism
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  • 52
    Publication Date: 1996-02-02
    Description: Hydrogen-deuterium exchange of 39 amide protons of Bacillus amyloliquefaciens ribonuclease (barnase) was analyzed by two-dimensional nuclear magnetic resonance in the presence of micromolar concentrations of the molecular chaperones GroEL and SecB. Both chaperones bound to native barnase under physiological conditions and catalyzed exchange of deeply buried amide protons with solvent. Such exchange required complete unfolding of barnase, which occurred in the complex with the chaperones. Subsequent collapse of unfolded barnase to the exchange-protected folding intermediate was markedly slowed in the presence of GroEL or SecB. Thus, both chaperones have the potential to correct misfolding in proteins by annealing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zahn, R -- Perrett, S -- Stenberg, G -- Fersht, A R -- New York, N.Y. -- Science. 1996 Feb 2;271(5249):642-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8571125" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/pharmacology ; Amides ; Bacterial Proteins/*metabolism ; Catalysis ; Chaperonin 60/*metabolism ; Hydrogen-Ion Concentration ; Kinetics ; Magnetic Resonance Spectroscopy ; Molecular Chaperones/*metabolism ; Protein Conformation ; *Protein Folding ; Protein Structure, Secondary ; *Protons ; Ribonucleases/*chemistry/metabolism ; Temperature
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  • 53
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-03-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaplan, J -- O'Halloran, T V -- R01 GM038784/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Mar 15;271(5255):1510-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of Utah School of Medicine, Salt Lake City, 84132, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8599104" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Biological Transport ; Carrier Proteins/genetics/*metabolism ; Ceruloplasmin/chemistry/*metabolism ; Copper/metabolism ; Ferric Compounds/metabolism ; Ferrous Compounds/metabolism ; Iron/*metabolism ; Membrane Transport Proteins/genetics/*metabolism ; Models, Molecular ; Oxidation-Reduction ; Oxidoreductases/*metabolism ; Protein Conformation ; Saccharomyces cerevisiae/genetics/*metabolism ; *Saccharomyces cerevisiae Proteins
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  • 54
    Publication Date: 1996-02-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lavigne, P -- Sonnichsen, F D -- Kay, C M -- Hodges, R S -- New York, N.Y. -- Science. 1996 Feb 23;271(5252):1136-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8599093" target="_blank"〉PubMed〈/a〉
    Keywords: *DNA-Binding Proteins ; Fungal Proteins/*chemistry ; Glutamic Acid/chemistry ; Glutamine/chemistry ; *Leucine Zippers ; Lysine/chemistry ; Protein Conformation ; Protein Folding ; Protein Kinases/*chemistry ; *Protein Structure, Secondary ; *Saccharomyces cerevisiae Proteins ; Thermodynamics
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  • 55
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-05-10
    Description: The molecular structure of the Escherichia coli RecA protein in the absence of DNA revealed two disordered or mobile loops that were proposed to be DNA binding sites. A short peptide spanning one of these loops was shown to carry out the key reaction mediated by the whole RecA protein: pairing (targeting) of a single-stranded DNA to its homologous site on a duplex DNA. In the course of the reaction the peptide bound to both substrate DNAs, unstacked the single-stranded DNA, and assumed a beta structure. These events probably recapitulate the underlying molecular pathway or mechanism used by homologous recombination proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Voloshin, O N -- Wang, L -- Camerini-Otero, R D -- New York, N.Y. -- Science. 1996 May 10;272(5263):868-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1810, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8629021" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; DNA, Single-Stranded/chemistry/genetics/*metabolism ; DNA, Superhelical/chemistry/genetics/*metabolism ; DNA-Binding Proteins/chemistry/metabolism ; Molecular Sequence Data ; Nucleic Acid Conformation ; Oligodeoxyribonucleotides/chemistry/metabolism ; Peptide Fragments/chemistry/*metabolism ; Protein Conformation ; Protein Structure, Secondary ; Rec A Recombinases/chemistry/*metabolism ; *Recombination, Genetic
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  • 56
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-06-14
    Description: Cysteine residues were introduced into three different positions distributed on the surface of ribosomal protein S5, to serve as targets for derivatization with an Fe(II)-ethyl-enediaminetetraacetic acid linker. Hydroxyl radicals generated locally from the tethered Fe(II) in intermediate ribonucleoprotein particles or in 30S ribosomal subunits reconstituted from derivatized S5 caused cleavage of the RNA, resulting in characteristically different cleavage patterns for the three different tethering positions. These findings provide constraints for the three-dimensional folding of 16S ribosomal RNA (rRNA) and for the orientation of S5 in the 30S subunit, and they further suggest that antibiotic resistance and accuracy mutations in S5 may involve perturbation of 16S rRNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heilek, G M -- Noller, H F -- New York, N.Y. -- Science. 1996 Jun 14;272(5268):1659-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Molecular Biology of RNA, Sinsheimer Laboratories, University of California, Santa Cruz 95064, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8658142" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-Bacterial Agents/pharmacology ; Cloning, Molecular ; Cysteine/chemistry ; Edetic Acid/analogs & derivatives ; Escherichia coli ; Ferrous Compounds/chemistry ; Hydroxyl Radical/*chemistry ; Models, Molecular ; Molecular Probes ; Mutagenesis, Site-Directed ; Nucleic Acid Conformation ; Organometallic Compounds ; Protein Conformation ; RNA, Ribosomal/*chemistry ; RNA, Ribosomal, 16S/chemistry/drug effects ; Ribosomal Proteins/*chemistry/genetics ; Spectinomycin/pharmacology
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  • 57
    Publication Date: 1996-06-14
    Description: The molybdoenzyme dimethylsulfoxide (DMSO) reductase contributes to the release of dimethylsulfide, a compound that has been implicated in cloud nucleation and global climate regulation. The crystal structure of DMSO reductase from Rhodobacter sphaeroides reveals a monooxo molybdenum cofactor containing two molybdopterin guanine dinucleotides that asymmetrically coordinate the molybdenum through their dithiolene groups. One of the pterins exhibits different coordination modes to the molybdenum between the oxidized and reduced states, whereas the side chain oxygen of Ser147 coordinates the metal in both states. The change in pterin coordination between the Mo(VI) and Mo(IV) forms suggests a mechanism for substrate binding and reduction by this enzyme. Sequence comparisons of DMSO reductase with a family of bacterial oxotransferases containing molybdopterin guanine dinucleotide indicate a similar polypeptide fold and active site with two molybdopterins within this family.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schindelin, H -- Kisker, C -- Hilton, J -- Rajagopalan, K V -- Rees, D C -- GM00091/GM/NIGMS NIH HHS/ -- GM50775/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Jun 14;272(5268):1615-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8658134" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Coenzymes/*chemistry ; Crystallography, X-Ray ; *Iron-Sulfur Proteins ; Metalloproteins/*chemistry ; Models, Molecular ; Molecular Sequence Data ; Oxidation-Reduction ; Oxidoreductases/*chemistry/metabolism ; Protein Conformation ; Pteridines/*chemistry ; Rhodobacter sphaeroides/*enzymology ; Sequence Homology, Amino Acid
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  • 58
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-02-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berendsen, H J -- New York, N.Y. -- Science. 1996 Feb 16;271(5251):954-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysical Chemistry, University of Groningen, Netherlands. berendsen@chem.rug.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8584930" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry ; Biotin/*chemistry ; Chemistry, Physical ; Computer Graphics ; *Computer Simulation ; Hydrogen Bonding ; Microscopy, Atomic Force ; *Models, Chemical ; Models, Molecular ; Molecular Conformation ; Physicochemical Phenomena ; Protein Conformation ; Streptavidin ; Thermodynamics
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  • 59
    Publication Date: 1996-03-01
    Description: The lac operon of Escherichia coli is the paradigm for gene regulation. Its key component is the lac repressor, a product of the lacI gene. The three-dimensional structures of the intact lac repressor, the lac repressor bound to the gratuitous inducer isopropyl-beta-D-1-thiogalactoside (IPTG) and the lac repressor complexed with a 21-base pair symmetric operator DNA have been determined. These three structures show the conformation of the molecule in both the induced and repressed states and provide a framework for understanding a wealth of biochemical and genetic information. The DNA sequence of the lac operon has three lac repressor recognition sites in a stretch of 500 base pairs. The crystallographic structure of the complex with DNA suggests that the tetrameric repressor functions synergistically with catabolite gene activator protein (CAP) and participates in the quaternary formation of repression loops in which one tetrameric repressor interacts simultaneously with two sites on the genomic DNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lewis, M -- Chang, G -- Horton, N C -- Kercher, M A -- Pace, H C -- Schumacher, M A -- Brennan, R G -- Lu, P -- 2-T32-GM082745/GM/NIGMS NIH HHS/ -- GM44617/GM/NIGMS NIH HHS/ -- P41-RR06017/RR/NCRR NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1996 Mar 1;271(5253):1247-54.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Johnson Research Foundation, University of Pennsylvania, Philadelphia 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8638105" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Bacterial Proteins/*chemistry/genetics/metabolism ; Base Sequence ; Binding Sites ; Crystallography, X-Ray ; Cyclic AMP Receptor Protein/metabolism ; DNA, Bacterial/chemistry/*metabolism ; *Escherichia coli Proteins ; Hydrogen Bonding ; Isopropyl Thiogalactoside/*metabolism ; *Lac Operon ; Lac Repressors ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Operator Regions, Genetic ; Point Mutation ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Repressor Proteins/*chemistry/genetics/metabolism
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  • 60
    Publication Date: 1996-09-06
    Description: A modulator of the enzymatic activity of human thrombin, designated LY254603, was identified that enhances the thrombin-catalyzed generation of the anticoagulant factor activated protein C, yet inhibits thrombin-dependent fibrinogen clotting. By means of mutant substrates, it was shown that LY254603 mediates the change in enzymatic substrate specificity through an alteration in thrombin's S3 substrate recognition site, a mechanism that appeared to be independent of allosteric changes induced by either sodium ions or by thrombomodulin. This compound may represent the prototype of a class of agents that specifically modulates the balance between thrombin's procoagulant and anticoagulant functions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berg, D T -- Wiley, M R -- Grinnell, B W -- New York, N.Y. -- Science. 1996 Sep 6;273(5280):1389-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiovascular Research Division, Lilly Research Laboratories, Indianapolis, IN 46285-0444, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8703074" target="_blank"〉PubMed〈/a〉
    Keywords: Blood Coagulation/drug effects ; Calcium/pharmacology ; Choline/pharmacology ; Dose-Response Relationship, Drug ; Enzyme Activation ; Fibrinogen/*metabolism ; Humans ; Naphthalenes/chemistry/*pharmacology ; Partial Thromboplastin Time ; Phenyl Ethers/chemistry/*pharmacology ; Protein C/chemistry/*metabolism ; Protein Conformation ; Recombinant Proteins/metabolism ; Sodium Chloride/pharmacology ; Substrate Specificity/drug effects ; Thrombin/*pharmacology ; Thrombomodulin/metabolism
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  • 61
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-02-23
    Description: Zinc ions are key structural components of a large number of proteins. The binding of zinc stabilizes the folded conformations of domains so that they may facilitate interactions between the proteins and other macromolecules such as DNA. The modular nature of some of these zinc-containing proteins has allowed the rational design of site-specific DNA binding proteins. The ability of zinc to be bound specifically within a range of tetrahedral sites appears to be responsible for the evolution of the side range of zinc-stabilized structural domains now known to exist. The lack of redox activity for the zinc ion and its binding and exchange kinetics also may be important in the use of zinc for specific functional roles.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berg, J M -- Shi, Y -- New York, N.Y. -- Science. 1996 Feb 23;271(5252):1081-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8599083" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; DNA/metabolism ; DNA-Binding Proteins/chemistry/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Engineering ; Transcription Factors/chemistry/*metabolism ; Zinc/chemistry/metabolism/*physiology ; Zinc Fingers/*physiology
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  • 62
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-12-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, E -- New York, N.Y. -- Science. 1996 Dec 6;274(5293):1613-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8984629" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Isomerases/physiology ; Carrier Proteins/*physiology ; *Cyclophilins ; DNA-Binding Proteins/physiology ; Fungal Proteins/*physiology ; HSP90 Heat-Shock Proteins/physiology ; Heat-Shock Proteins/physiology ; Molecular Chaperones/*physiology ; *Peptidylprolyl Isomerase ; Protein Conformation ; Protein Denaturation ; *Protein Folding ; Signal Transduction ; Tacrolimus Binding Proteins
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  • 63
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-10-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Service, R F -- New York, N.Y. -- Science. 1996 Oct 11;274(5285):176-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8927977" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Crystallography, X-Ray ; Drosophila melanogaster ; H-2 Antigens/*chemistry/immunology/metabolism ; Killer Cells, Natural/immunology ; *Major Histocompatibility Complex ; Models, Molecular ; Peptides/immunology/metabolism ; Protein Conformation ; Receptors, Antigen, T-Cell, alpha-beta/*chemistry/immunology/metabolism ; Recombinant Proteins/chemistry ; T-Lymphocytes, Cytotoxic/*immunology
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  • 64
    Publication Date: 1996-06-14
    Description: DnaK and other members of the 70-kilodalton heat-shock protein (hsp70) family promote protein folding, interaction, and translocation, both constitutively and in response to stress, by binding to unfolded polypeptide segments. These proteins have two functional units: a substrate-binding portion binds the polypeptide, and an adenosine triphosphatase portion facilitates substrate exchange. The crystal structure of a peptide complex with the substrate-binding unit of DnaK has now been determined at 2.0 angstroms resolution. The structure consists of a beta-sandwich subdomain followed by alpha-helical segments. The peptide is bound to DnaK in an extended conformation through a channel defined by loops from the beta sandwich. An alpha-helical domain stabilizes the complex, but does not contact the peptide directly. This domain is rotated in the molecules of a second crystal lattice, which suggests a model of conformation-dependent substrate binding that features a latch mechanism for maintaining long lifetime complexes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhu, X -- Zhao, X -- Burkholder, W F -- Gragerov, A -- Ogata, C M -- Gottesman, M E -- Hendrickson, W A -- GM 34102/GM/NIGMS NIH HHS/ -- GM 37219/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Jun 14;272(5268):1606-14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8658133" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Chaperonins/chemistry/*metabolism ; Crystallography, X-Ray ; Escherichia coli ; *Escherichia coli Proteins ; HSP70 Heat-Shock Proteins/chemistry/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Peptides/metabolism ; Protein Binding ; Protein Conformation ; Sequence Homology, Amino Acid
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  • 65
    Publication Date: 1996-10-25
    Description: Histone-DNA contacts within a nucleosome influence the function of trans-acting factors and the molecular machines required to activate the transcription process. The internal architecture of a positioned nucleosome has now been probed with the use of photoactivatable cross-linking reagents to determine the placement of histones along the DNA molecule. A model for the nucleosome is proposed in which the winged-helix domain of the linker histone is asymmetrically located inside the gyres of DNA that also wrap around the core histones. This domain extends the path of the protein superhelix to one side of the core particle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pruss, D -- Bartholomew, B -- Persinger, J -- Hayes, J -- Arents, G -- Moudrianakis, E N -- Wolffe, A P -- New York, N.Y. -- Science. 1996 Oct 25;274(5287):614-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2710, USA. awlme@helix.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8849453" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Cross-Linking Reagents ; DNA/*chemistry/metabolism ; Histones/*chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Nucleosomes/*chemistry ; Protein Conformation ; Protein Structure, Secondary ; RNA, Ribosomal/genetics ; Recombinant Proteins/chemistry ; Xenopus
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  • 66
    Publication Date: 1996-02-16
    Description: The force required to rupture the streptavidin-biotin complex was calculated here by computer simulations. The computed force agrees well with that obtained by recent single molecule atomic force microscope experiments. These simulations suggest a detailed multiple-pathway rupture mechanism involving five major unbinding steps. Binding forces and specificity are attributed to a hydrogen bond network between the biotin ligand and residues within the binding pocket of streptavidin. During rupture, additional water bridges substantially enhance the stability of the complex and even dominate the binding interactions. In contrast, steric restraints do not appear to contribute to the binding forces, although conformational motions were observed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grubmuller, H -- Heymann, B -- Tavan, P -- New York, N.Y. -- Science. 1996 Feb 16;271(5251):997-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Theoretische Biophysik, Institut fur Medizinische Optik, Ludwig- Maximilians-Universitat Munchen, Germany. Helmut.Grubmueller@ Physik.uni-muenchen.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8584939" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry ; Biotin/*chemistry ; Chemistry, Physical ; *Computer Simulation ; Hydrogen Bonding ; Ligands ; Microscopy, Atomic Force ; *Models, Chemical ; Molecular Conformation ; Physicochemical Phenomena ; Protein Conformation ; Streptavidin ; Thermodynamics
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  • 67
    Publication Date: 1996-07-12
    Description: C2 domains are found in many proteins involved in membrane traffic or signal transduction. Although C2 domains are thought to bind calcium ions, the structural basis for calcium binding is unclear. Analysis of calcium binding to C2 domains of synaptotagmin I and protein kinase C-beta by nuclear magnetic resonance spectroscopy revealed a bipartite calcium-binding motif that involves the coordination of two calcium ions by five aspartate residues located on two separate loops. Sequence comparisons indicated that this may be a widely used calcium-binding motif, designated here as the C2 motif.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shao, X -- Davletov, B A -- Sutton, R B -- Sudhof, T C -- Rizo, J -- R01-MH52804-01/MH/NIMH NIH HHS/ -- R29 NS33731-01A1/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1996 Jul 12;273(5272):248-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8662510" target="_blank"〉PubMed〈/a〉
    Keywords: Aspartic Acid/chemistry ; Base Sequence ; Calcium/*metabolism ; *Calcium-Binding Proteins ; Crystallography, X-Ray ; Hydrogen-Ion Concentration ; Magnetic Resonance Spectroscopy ; Membrane Glycoproteins/*chemistry/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Nerve Tissue Proteins/*chemistry/*metabolism ; Phospholipids/metabolism ; Protein Conformation ; Protein Folding ; Protein Kinase C/chemistry/*metabolism ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Synaptotagmin I ; Synaptotagmins ; Temperature
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  • 68
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-08-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fischman, J -- New York, N.Y. -- Science. 1996 Aug 2;273(5275):591-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8701313" target="_blank"〉PubMed〈/a〉
    Keywords: *Amino Acid Sequence ; *Base Sequence ; *Computer Communication Networks ; DNA/*genetics ; *Information Systems ; Models, Molecular ; *Programming Languages ; Protein Conformation ; Proteins/chemistry
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  • 69
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-07-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Service, R F -- New York, N.Y. -- Science. 1996 Jul 5;273(5271):29-30.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8658186" target="_blank"〉PubMed〈/a〉
    Keywords: Apoproteins/*chemistry ; Fluorescence ; Lasers ; Myoglobin/*chemistry ; Protein Conformation ; Protein Denaturation ; *Protein Folding ; Protein Structure, Secondary ; Temperature ; Ultraviolet Rays
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  • 70
    Publication Date: 1996-07-26
    Description: The functional mimicry of a protein by an unrelated small molecule has been a formidable challenge. Now, however, the biological activity of a 166-residue hematopoietic growth hormone, erythropoietin (EPO), with its class 1 cytokine receptor has been mimicked by a 20-residue cyclic peptide unrelated in sequence to the natural ligand. The crystal structure at 2.8 A resolution of a complex of this agonist peptide with the extracellular domain of EPO receptor reveals that a peptide dimer induces an almost perfect twofold dimerization of the receptor. The dimer assembly differs from that of the human growth hormone (hGH) receptor complex and suggests that more than one mode of dimerization may be able to induce signal transduction and cell proliferation. The EPO receptor binding site, defined by peptide interaction, corresponds to the smaller functional epitope identified for hGH receptor. Similarly, the EPO mimetic peptide ligand can be considered as a minimal hormone, and suggests the design of nonpeptidic small molecule mimetics for EPO and other cytokines may indeed be achievable.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Livnah, O -- Stura, E A -- Johnson, D L -- Middleton, S A -- Mulcahy, L S -- Wrighton, N C -- Dower, W J -- Jolliffe, L K -- Wilson, I A -- GM-49497/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Jul 26;273(5274):464-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and the Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10666 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/8662530" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Crystallography, X-Ray ; Drug Design ; Erythropoietin/*chemistry/*metabolism ; Growth Hormone/chemistry/metabolism ; Humans ; Hydrogen Bonding ; Models, Molecular ; *Molecular Mimicry ; Molecular Sequence Data ; Peptides, Cyclic/*chemistry/*metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Receptors, Erythropoietin/*agonists/chemistry/metabolism ; Receptors, Somatotropin/chemistry/metabolism
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  • 71
    Publication Date: 1996-02-23
    Description: Crystal structures of heparin-derived tetra- and hexasaccharides complexed with basic fibroblast growth factor (bFGF) were determined at resolutions of 1.9 and 2.2 angstroms, respectively. The heparin structure may be approximated as a helical polymer with a disaccharide rotation of 174 degrees and a translation of 8.6 angstroms along the helix axis. Both molecules bound similarly to a region of the bFGF surface containing residues asparagine-28, arginine-121, lysine-126, and glutamine-135, the hexasaccharide also interacted with an additional binding site formed by lysine-27, asparagine-102, and lysine-136. No significant conformational change in bFGF occurred upon heparin oligosaccharide binding, which suggests that heparin primarily serves to juxtapose components of the FGF signal transduction pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Faham, S -- Hileman, R E -- Fromm, J R -- Linhardt, R J -- Rees, D C -- GM38060/GM/NIGMS NIH HHS/ -- GM45162/GM/NIGMS NIH HHS/ -- T32 GM08346/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Feb 23;271(5252):1116-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8599088" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Carbohydrate Conformation ; Carbohydrate Sequence ; Crystallization ; Crystallography, X-Ray ; Fibroblast Growth Factor 2/*metabolism ; Heparin/*chemistry/metabolism ; Hydrogen Bonding ; Models, Molecular ; Molecular Sequence Data ; Oligosaccharides/chemistry/metabolism ; Protein Conformation
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  • 72
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-06-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stiefel, E I -- New York, N.Y. -- Science. 1996 Jun 14;272(5268):1599-600.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Exxon Research and Engineering Company in Clinton Township, Annandale, New Jersey 08807, USA. eistief@erenj.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8658132" target="_blank"〉PubMed〈/a〉
    Keywords: Coenzymes/metabolism ; *Iron-Sulfur Proteins ; Metalloproteins/metabolism ; Molybdenum/*metabolism ; Oceans and Seas ; Oxidoreductases/chemistry/*metabolism ; Protein Conformation ; Pteridines/metabolism ; Sulfides/metabolism
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  • 73
    Publication Date: 1996-10-18
    Description: Many transmembrane receptors are oligomeric proteins. Binding of a ligand may alter the oligomeric state of the receptor, induce structural changes within the oligomer, or both. The bacterial aspartate chemoreceptor Tar forms a homodimer in the presence or absence of ligands. Tar mediates attractant and repellent responses by modulating the activity of the cytoplasmic kinase CheA. In vivo intersubunit suppression was used to show that certain combinations of full-length and truncated mutant Tar proteins complemented each other to restore attractant responses to aspartate. These results suggest that heterodimers with only one intact cytoplasmic domain are functional. The signaling mechanism may require interactions between dimers or conformational changes within a single cytoplasmic domain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tatsuno, I -- Homma, M -- Oosawa, K -- Kawagishi, I -- New York, N.Y. -- Science. 1996 Oct 18;274(5286):423-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-01, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8832891" target="_blank"〉PubMed〈/a〉
    Keywords: Aspartic Acid/*metabolism/pharmacology ; Bacterial Proteins/chemistry/genetics/*metabolism ; Chemoreceptor Cells ; Chemotaxis ; Cytoplasm/metabolism ; Dimerization ; Escherichia coli/genetics/*metabolism/physiology ; *Escherichia coli Proteins ; Glycerol/pharmacology ; Membrane Proteins/chemistry/genetics/*metabolism ; Methylation ; Mutation ; Protein Conformation ; Protein Kinases/metabolism ; Receptors, Cell Surface/chemistry/genetics/*metabolism ; Signal Transduction/*physiology ; Suppression, Genetic
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  • 74
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-10-18
    Description: Signal transduction across cell membranes often involves interactions among identical receptor subunits, but the contribution of individual subunits is not well understood. The chemoreceptors of enteric bacteria mediate attractant responses by interrupting a phosphotransfer circuit initiated at receptor complexes with the protein kinase CheA. The aspartate receptor (Tar) is a homodimer, and oligomerized cytoplasmic domains stimulate CheA activity much more than monomers do in vitro. Intragenic complementation was used to show in Escherichia coli that heterodimers containing one full-length and one truncated Tar subunit mediated responses to aspartate in the presence of full-length Tar homodimers that could not bind aspartate. Thus, a Tar dimer containing only one cytoplasmic domain can initiate an attractant (inhibitory) signal, although it may not be able to stimulate kinase activity of CheA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gardina, P J -- Manson, M D -- GM39736/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Oct 18;274(5286):425-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Texas A&M University, College Station, TX 77840, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8832892" target="_blank"〉PubMed〈/a〉
    Keywords: Aspartic Acid/*metabolism/pharmacology ; Bacterial Proteins/chemistry/genetics/*metabolism ; Binding Sites ; Chemoreceptor Cells ; Chemotaxis ; Cytoplasm/metabolism ; Dimerization ; Escherichia coli/genetics/*metabolism/physiology ; *Escherichia coli Proteins ; Genetic Complementation Test ; Membrane Proteins/chemistry/genetics/*metabolism ; Mutation ; Plasmids ; Protein Conformation ; Protein Kinases/metabolism ; Receptors, Cell Surface/chemistry/genetics/*metabolism ; Signal Transduction/*physiology
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  • 75
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-05-10
    Description: The crystal structure of the yeast TFIIA/TBP/TATA promoter complex was solved to 3 angstrom resolution by double-edge multiple wavelength anomalous diffraction from two different species of anomalous scattering elements in the same crystal. The large and small subunits of TFIIA associate intimately to form both domains of a two-domain folding pattern. TFIIA binds as a heterodimer to the side of the TBP/TATA complex opposite to the side that binds TFIIB and does not alter the TBP/DNA interaction. The six-stranded beta-sandwich domain interacts with the amino-terminal end of TBP through a stereospecific parallel beta-strand interface and with the backbone of the TATA box and the 5'-flanking B-DNA segment. The four-helix-bundle domain projects away from the TBP/TATA complex, thereby presenting a substantial surface for further protein-protein interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geiger, J H -- Hahn, S -- Lee, S -- Sigler, P B -- New York, N.Y. -- Science. 1996 May 10;272(5263):830-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8629014" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Crystallography, X-Ray ; DNA, Fungal/*chemistry/metabolism ; DNA-Binding Proteins/*chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis ; Nucleic Acid Conformation ; Promoter Regions, Genetic ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Saccharomyces cerevisiae/chemistry/genetics/metabolism ; TATA Box ; TATA-Box Binding Protein ; Transcription Factor TFIIA ; Transcription Factor TFIIB ; Transcription Factors/*chemistry/metabolism ; Transcription, Genetic
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  • 76
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-03-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matthews, K S -- New York, N.Y. -- Science. 1996 Mar 1;271(5253):1245-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77251, USA. ksm@bioc.vice.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8638104" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Bacterial Proteins/*chemistry/genetics/metabolism ; Binding Sites ; Crystallography, X-Ray ; DNA, Bacterial/metabolism ; *Escherichia coli Proteins ; Isopropyl Thiogalactoside/metabolism ; Lac Operon ; Lac Repressors ; Ligands ; Mutagenesis ; Operator Regions, Genetic ; Protein Conformation ; Protein Folding ; Repressor Proteins/*chemistry/genetics/metabolism
    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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  • 77
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-05-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferguson-Miller, S -- New York, N.Y. -- Science. 1996 May 24;272(5265):1125.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Michigan State University, East Lansing, MI 48824-1319, USA. fergus20@pilot.msu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8638156" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Cattle ; Electron Transport Complex IV/*chemistry/metabolism ; Molecular Weight ; Protein Conformation ; Protons ; X-Ray Diffraction
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 78
    Publication Date: 1996-02-23
    Description: The germline genes used by the mouse to generate the esterolytic antibody 48G7 were cloned and expressed in an effort to increase our understanding of the detailed molecular mechanisms by which the immune system evolves catalytic function. The nine replacement mutations that were fixed during affinity maturation increased affinity for the transition state analogue by a factor of 10(4), primarily the result of a decrease in the dissociation rate of the hapten-antibody complex. There was a corresponding increase in the rate of reaction of antibody with substrate, k(cat)/k(m), from 1.7 x 10(2)M(-1) min(-1) to 1.4 x 10(4)M(-1) min(-1). The three-dimensional crystal structure of the 48G7-transition state analogue complex at 2.0 angstroms resolution indicates that one of the nine residues in which somatic mutations have been fixed directly contact the hapten. Thus, in the case of 48G7, affinity maturation appears to play a conformational role, either in reorganizing the active site geometry of limiting side-chain and backbone flexibility of the germline antibody. The crystal structure and analysis of somatic and directed active site mutants underscore the role of transition state stabilization in the evolution of this catalytic antibody.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Patten, P A -- Gray, N S -- Yang, P L -- Marks, C B -- Wedemayer, G J -- Boniface, J J -- Stevens, R C -- Schultz, P G -- R01 AL24695/PHS HHS/ -- New York, N.Y. -- Science. 1996 Feb 23;271(5252):1086-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Chemistry, University of California, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8599084" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antibodies, Catalytic/chemistry/genetics/*immunology/metabolism ; Antibody Affinity ; Antigen-Antibody Complex ; Antigen-Antibody Reactions ; Base Sequence ; Binding Sites ; Catalysis ; Cloning, Molecular ; Crystallization ; Crystallography, X-Ray ; *Evolution, Molecular ; Genes, Immunoglobulin ; Haptens/immunology ; Immunoglobulin Fab Fragments/genetics/immunology ; Immunoglobulin Heavy Chains/genetics/immunology ; Immunoglobulin Light Chains/genetics/immunology ; Mice ; Molecular Sequence Data ; Mutation ; Protein Conformation
    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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  • 79
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-03-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weinstein, H -- Mehler, E L -- New York, N.Y. -- Science. 1996 Mar 29;271(5257):1792-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8596942" target="_blank"〉PubMed〈/a〉
    Keywords: Arginine/chemistry ; Calmodulin/*chemistry/metabolism ; Computer Simulation ; Hydrogen Bonding ; Mutation ; Protein Conformation ; Troponin/*chemistry/genetics/metabolism ; Troponin C
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 80
    Publication Date: 1996-05-17
    Description: The high-resolution x-ray crystal structures of the murine major histocompatibility complex (MHC) class II molecule, I-E(k), occupied by either of two antigenic peptides were determined. They reveal the structural basis for the I-E(k) peptide binding motif and suggest general principles for additional alleles. A buried cluster of acidic amino acids in the binding groove predicted to be conserved among all murine I-E and human DR MHC class II molecules suggests how pH may influence MHC binding or exchange of peptides. These structures also complement mutational studies on the importance of individual peptide residues to T cell receptor recognition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fremont, D H -- Hendrickson, W A -- Marrack, P -- Kappler, J -- New York, N.Y. -- Science. 1996 May 17;272(5264):1001-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8638119" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/chemistry ; Animals ; Antigen Presentation ; Antigens/*chemistry/immunology/metabolism ; Crystallography, X-Ray ; HLA-DR Antigens/chemistry/immunology/metabolism ; HSP70 Heat-Shock Proteins/chemistry ; Hemoglobins/chemistry ; Histocompatibility Antigens Class II/*chemistry/immunology/metabolism ; Humans ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Mice ; Models, Molecular ; Molecular Sequence Data ; Peptide Fragments/*chemistry/immunology/metabolism ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Receptors, Antigen, T-Cell/metabolism
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 81
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-12-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fried, M G -- Hudson, J M -- New York, N.Y. -- Science. 1996 Dec 13;274(5294):1930-1; author reply 1931-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8984648" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/chemistry/*metabolism ; Binding Sites ; Cyclic AMP Receptor Protein/chemistry/*metabolism ; DNA, Bacterial/chemistry/*metabolism ; Escherichia coli/genetics ; *Escherichia coli Proteins ; *Lac Operon ; Lac Repressors ; *Nucleic Acid Conformation ; Operator Regions, Genetic ; Protein Binding ; Protein Conformation ; Repressor Proteins/chemistry/*metabolism
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 82
    Publication Date: 1996-06-14
    Description: The basal cell nevus syndrome (BCNS) is characterized by developmental abnormalities and by the postnatal occurrence of cancers, especially basal cell carcinomas (BCCs), the most common human cancer. Heritable mutations in BCNS patients and a somatic mutation in a sporadic BCC were identified in a human homolog of the Drosophila patched (ptc) gene. The ptc gene encodes a transmembrane protein that in Drosophila acts in opposition to the Hedgehog signaling protein, controlling cell fates, patterning, and growth in numerous tissues. The human PTC gene appears to be crucial for proper embryonic development and for tumor suppression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, R L -- Rothman, A L -- Xie, J -- Goodrich, L V -- Bare, J W -- Bonifas, J M -- Quinn, A G -- Myers, R M -- Cox, D R -- Epstein, E H Jr -- Scott, M P -- AR3995/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 1996 Jun 14;272(5268):1668-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology, Howard Hughes Medical Institute, Stanford University School of Medicine, California 94305-5427, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8658145" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Amino Acid Sequence ; Animals ; Basal Cell Nevus Syndrome/*genetics ; Base Sequence ; Cloning, Molecular ; DNA, Neoplasm ; Drosophila ; *Drosophila Proteins ; Female ; Frameshift Mutation ; *Genes, Tumor Suppressor ; Humans ; Insect Hormones/genetics ; Male ; Membrane Proteins/*genetics ; Middle Aged ; Molecular Sequence Data ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Protein Conformation ; Receptors, Cell Surface
    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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