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  • Binding Sites
  • American Association for the Advancement of Science (AAAS)  (7)
  • 2010-2014  (7)
  • 1995-1999
  • 1980-1984
  • 1970-1974
  • 2012  (7)
Collection
Publisher
Years
  • 2010-2014  (7)
  • 1995-1999
  • 1980-1984
  • 1970-1974
Year
  • 1
    Publication Date: 2012-04-21
    Description: Salicylate, a plant product, has been in medicinal use since ancient times. More recently, it has been replaced by synthetic derivatives such as aspirin and salsalate, both of which are rapidly broken down to salicylate in vivo. At concentrations reached in plasma after administration of salsalate or of aspirin at high doses, salicylate activates adenosine monophosphate-activated protein kinase (AMPK), a central regulator of cell growth and metabolism. Salicylate binds at the same site as the synthetic activator A-769662 to cause allosteric activation and inhibition of dephosphorylation of the activating phosphorylation site, threonine-172. In AMPK knockout mice, effects of salicylate to increase fat utilization and to lower plasma fatty acids in vivo were lost. Our results suggest that AMPK activation could explain some beneficial effects of salsalate and aspirin in humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399766/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399766/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hawley, Simon A -- Fullerton, Morgan D -- Ross, Fiona A -- Schertzer, Jonathan D -- Chevtzoff, Cyrille -- Walker, Katherine J -- Peggie, Mark W -- Zibrova, Darya -- Green, Kevin A -- Mustard, Kirsty J -- Kemp, Bruce E -- Sakamoto, Kei -- Steinberg, Gregory R -- Hardie, D Grahame -- 080982/Wellcome Trust/United Kingdom -- 097726/Wellcome Trust/United Kingdom -- MC_U127088492/Medical Research Council/United Kingdom -- Canadian Institutes of Health Research/Canada -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2012 May 18;336(6083):918-22. doi: 10.1126/science.1215327. Epub 2012 Apr 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22517326" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/genetics/*metabolism ; Amino Acid Substitution ; Animals ; Aspirin/pharmacology ; Binding Sites ; Carbohydrate Metabolism/drug effects ; Cell Line ; Enzyme Activation ; Enzyme Activators/pharmacology ; HEK293 Cells ; Humans ; Lipid Metabolism/drug effects ; Liver/drug effects/metabolism ; Mice ; Mice, Knockout ; Mutation ; Oxygen Consumption/drug effects ; Phosphorylation ; Pyrones/pharmacology ; Rats ; Salicylates/blood/*metabolism/*pharmacology ; Thiophenes/pharmacology
    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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  • 2
    Publication Date: 2012-03-03
    Description: Bacteria adapt to environmental stimuli by adjusting their transcriptomes in a complex manner, the full potential of which has yet to be established for any individual bacterial species. Here, we report the transcriptomes of Bacillus subtilis exposed to a wide range of environmental and nutritional conditions that the organism might encounter in nature. We comprehensively mapped transcription units (TUs) and grouped 2935 promoters into regulons controlled by various RNA polymerase sigma factors, accounting for ~66% of the observed variance in transcriptional activity. This global classification of promoters and detailed description of TUs revealed that a large proportion of the detected antisense RNAs arose from potentially spurious transcription initiation by alternative sigma factors and from imperfect control of transcription termination.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nicolas, Pierre -- Mader, Ulrike -- Dervyn, Etienne -- Rochat, Tatiana -- Leduc, Aurelie -- Pigeonneau, Nathalie -- Bidnenko, Elena -- Marchadier, Elodie -- Hoebeke, Mark -- Aymerich, Stephane -- Becher, Dorte -- Bisicchia, Paola -- Botella, Eric -- Delumeau, Olivier -- Doherty, Geoff -- Denham, Emma L -- Fogg, Mark J -- Fromion, Vincent -- Goelzer, Anne -- Hansen, Annette -- Hartig, Elisabeth -- Harwood, Colin R -- Homuth, Georg -- Jarmer, Hanne -- Jules, Matthieu -- Klipp, Edda -- Le Chat, Ludovic -- Lecointe, Francois -- Lewis, Peter -- Liebermeister, Wolfram -- March, Anika -- Mars, Ruben A T -- Nannapaneni, Priyanka -- Noone, David -- Pohl, Susanne -- Rinn, Bernd -- Rugheimer, Frank -- Sappa, Praveen K -- Samson, Franck -- Schaffer, Marc -- Schwikowski, Benno -- Steil, Leif -- Stulke, Jorg -- Wiegert, Thomas -- Devine, Kevin M -- Wilkinson, Anthony J -- van Dijl, Jan Maarten -- Hecker, Michael -- Volker, Uwe -- Bessieres, Philippe -- Noirot, Philippe -- New York, N.Y. -- Science. 2012 Mar 2;335(6072):1103-6. doi: 10.1126/science.1206848.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INRA, UR1077, Mathematique Informatique et Genome, Jouy-en-Josas, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22383849" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Algorithms ; Bacillus subtilis/*genetics/*physiology ; Binding Sites ; Gene Expression Profiling ; *Gene Expression Regulation, Bacterial ; Gene Regulatory Networks ; Oligonucleotide Array Sequence Analysis ; *Promoter Regions, Genetic ; RNA, Antisense/genetics/metabolism ; RNA, Bacterial/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Regulon ; Sigma Factor/metabolism ; Terminator Regions, Genetic ; *Transcription, Genetic ; *Transcriptome
    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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  • 3
    Publication Date: 2012-02-11
    Description: Sodium/calcium (Na(+)/Ca(2+)) exchangers (NCX) are membrane transporters that play an essential role in maintaining the homeostasis of cytosolic Ca(2+) for cell signaling. We demonstrated the Na(+)/Ca(2+)-exchange function of an NCX from Methanococcus jannaschii (NCX_Mj) and report its 1.9 angstrom crystal structure in an outward-facing conformation. Containing 10 transmembrane helices, the two halves of NCX_Mj share a similar structure with opposite orientation. Four ion-binding sites cluster at the center of the protein: one specific for Ca(2+) and three that likely bind Na(+). Two passageways allow for Na(+) and Ca(2+) access to the central ion-binding sites from the extracellular side. Based on the symmetry of NCX_Mj and its ability to catalyze bidirectional ion-exchange reactions, we propose a structure model for the inward-facing NCX_Mj.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liao, Jun -- Li, Hua -- Zeng, Weizhong -- Sauer, David B -- Belmares, Ricardo -- Jiang, Youxing -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Feb 10;335(6069):686-90. doi: 10.1126/science.1215759.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22323814" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Archaeal Proteins/*chemistry/metabolism ; Binding Sites ; Calcium/*metabolism ; Crystallization ; Crystallography, X-Ray ; Ion Transport ; Ligands ; Methanococcales/*chemistry/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Structure, Secondary ; Sodium/*metabolism ; Sodium-Calcium Exchanger/*chemistry/*metabolism
    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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  • 4
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2012-11-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schubeler, Dirk -- New York, N.Y. -- Science. 2012 Nov 9;338(6108):756-7. doi: 10.1126/science.1227243.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland. dirk@fmi.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23139324" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; *CpG Islands ; *DNA Methylation ; DNA-Binding Proteins/metabolism ; Enhancer Elements, Genetic ; *Epigenesis, Genetic ; *Gene Expression Regulation ; Humans ; Promoter Regions, Genetic ; Transcription Factors/metabolism
    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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  • 5
    Publication Date: 2012-06-02
    Description: C99 is the transmembrane carboxyl-terminal domain of the amyloid precursor protein that is cleaved by gamma-secretase to release the amyloid-beta polypeptides, which are associated with Alzheimer's disease. Nuclear magnetic resonance and electron paramagnetic resonance spectroscopy show that the extracellular amino terminus of C99 includes a surface-embedded "N-helix" followed by a short "N-loop" connecting to the transmembrane domain (TMD). The TMD is a flexibly curved alpha helix, making it well suited for processive cleavage by gamma-secretase. Titration of C99 reveals a binding site for cholesterol, providing mechanistic insight into how cholesterol promotes amyloidogenesis. Membrane-buried GXXXG motifs (G, Gly; X, any amino acid), which have an established role in oligomerization, were also shown to play a key role in cholesterol binding. The structure and cholesterol binding properties of C99 may aid in the design of Alzheimer's therapeutics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528355/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528355/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barrett, Paul J -- Song, Yuanli -- Van Horn, Wade D -- Hustedt, Eric J -- Schafer, Johanna M -- Hadziselimovic, Arina -- Beel, Andrew J -- Sanders, Charles R -- F31 NS077681/NS/NINDS NIH HHS/ -- P01 GM080513/GM/NIGMS NIH HHS/ -- T32 GM008320/GM/NIGMS NIH HHS/ -- T32 GM08320/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Jun 1;336(6085):1168-71. doi: 10.1126/science.1219988.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Center for Structural Biology and Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, TN 37232 USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22654059" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Amyloid beta-Protein Precursor/*chemistry/genetics/*metabolism ; Binding Sites ; Cholesterol/*metabolism ; Electron Spin Resonance Spectroscopy ; Humans ; Micelles ; Molecular Sequence Data ; Mutation ; Nuclear Magnetic Resonance, Biomolecular ; Peptide Fragments/*chemistry/genetics/*metabolism ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2012-11-20
    Description: The epicardium encapsulates the heart and functions as a source of multipotent progenitor cells and paracrine factors essential for cardiac development and repair. Injury of the adult heart results in reactivation of a developmental gene program in the epicardium, but the transcriptional basis of epicardial gene expression has not been delineated. We established a mouse embryonic heart organ culture and gene expression system that facilitated the identification of epicardial enhancers activated during heart development and injury. Epicardial activation of these enhancers depends on a combinatorial transcriptional code centered on CCAAT/enhancer binding protein (C/EBP) transcription factors. Disruption of C/EBP signaling in the adult epicardium reduced injury-induced neutrophil infiltration and improved cardiac function. These findings reveal a transcriptional basis for epicardial activation and heart injury, providing a platform for enhancing cardiac regeneration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613149/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613149/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Guo N -- Thatcher, Jeffrey E -- McAnally, John -- Kong, Yongli -- Qi, Xiaoxia -- Tan, Wei -- DiMaio, J Michael -- Amatruda, James F -- Gerard, Robert D -- Hill, Joseph A -- Bassel-Duby, Rhonda -- Olson, Eric N -- 1K99HL114738/HL/NHLBI NIH HHS/ -- HL100401-01/HL/NHLBI NIH HHS/ -- K99 HL114738/HL/NHLBI NIH HHS/ -- R01 HL077439/HL/NHLBI NIH HHS/ -- R01 HL093039/HL/NHLBI NIH HHS/ -- R01 HL111665/HL/NHLBI NIH HHS/ -- U01 HL100401/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2012 Dec 21;338(6114):1599-603. doi: 10.1126/science.1229765. Epub 2012 Nov 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23160954" target="_blank"〉PubMed〈/a〉
    Keywords: Aldehyde Oxidoreductases/genetics/metabolism ; Animals ; Binding Sites ; CCAAT-Enhancer-Binding Protein-beta/genetics/metabolism ; CCAAT-Enhancer-Binding Protein-delta/genetics/metabolism ; CCAAT-Enhancer-Binding Proteins/genetics/*metabolism ; Enhancer Elements, Genetic ; Female ; *Gene Expression Regulation ; Gene Expression Regulation, Developmental ; Heart/embryology/*physiopathology ; Male ; Mice ; Mice, Transgenic ; Models, Genetic ; Myocardial Contraction ; Myocardial Infarction/*genetics/metabolism ; Myocardial Reperfusion Injury/*genetics/metabolism ; Neutrophil Infiltration ; Oligonucleotide Array Sequence Analysis ; Organ Culture Techniques ; Pericardium/cytology/*embryology/*metabolism ; Signal Transduction ; Uroplakin III/genetics/metabolism ; Ventricular Remodeling ; WT1 Proteins/genetics/metabolism
    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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  • 7
    Publication Date: 2012-06-02
    Description: Wnts are lipid-modified morphogens that play critical roles in development principally through engagement of Frizzled receptors. The 3.25 angstrom structure of Xenopus Wnt8 (XWnt8) in complex with mouse Frizzled-8 (Fz8) cysteine-rich domain (CRD) reveals an unusual two-domain Wnt structure, not obviously related to known protein folds, resembling a "hand" with "thumb" and "index" fingers extended to grasp the Fz8-CRD at two distinct binding sites. One site is dominated by a palmitoleic acid lipid group projecting from serine 187 at the tip of Wnt's thumb into a deep groove in the Fz8-CRD. In the second binding site, the conserved tip of Wnt's "index finger" forms hydrophobic amino acid contacts with a depression on the opposite side of the Fz8-CRD. The conservation of amino acids in both interfaces appears to facilitate ligand-receptor cross-reactivity, which has important implications for understanding Wnt's functional pleiotropy and for developing Wnt-based drugs for cancer and regenerative medicine.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577348/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577348/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Janda, Claudia Y -- Waghray, Deepa -- Levin, Aron M -- Thomas, Christoph -- Garcia, K Christopher -- R01 GM097015/GM/NIGMS NIH HHS/ -- R01-GM097015/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Jul 6;337(6090):59-64. doi: 10.1126/science.1222879. Epub 2012 May 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22653731" target="_blank"〉PubMed〈/a〉
    Keywords: Acylation ; Amino Acid Sequence ; Animals ; Binding Sites ; Crystallography, X-Ray ; Cysteine/chemistry ; Fatty Acids, Monounsaturated/chemistry ; Glycosylation ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Mice ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; Protein Folding ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, G-Protein-Coupled/*chemistry/metabolism ; Recombinant Proteins/chemistry/metabolism ; Wnt Proteins/*chemistry/metabolism ; Wnt Signaling Pathway ; Xenopus Proteins/*chemistry/metabolism ; Xenopus laevis
    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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