4bvg: Difference between revisions

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 <StructureSection load='4bvg' size='340' side='right'caption='[[4bvg]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4bvg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BVG OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=4BVG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4bvg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BVG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BVG FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=XYQ:(2R,3R,4S,5R)-5-({[(R)-{[(R)-{[(2R,3S,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-3,4-DIHYDROXYTETRAHYDROFURAN-2-YL]METHOXY}(HYDROXY)PHOSPHORYL]OXY}(HYDROXY)PHOSPHORYL]OXY}METHYL)-3,4-DIHYDROXYTETRAHYDROFURAN-2-YL+ACETATE'>XYQ</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bv2|4bv2]], [[4bv3|4bv3]], [[4bvb|4bvb]], [[4bve|4bve]], [[4bvf|4bvf]], [[4bvh|4bvh]], [[4buz|4buz]]</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4bvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bvg OCA], [https://pdbe.org/4bvg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bvg RCSB], [https://www.ebi.ac.uk/pdbsum/4bvg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bvg ProSAT]</span></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acetate--CoA_ligase Acetate--CoA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.2.1.1 6.2.1.1] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=4bvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bvg OCA], [http://pdbe.org/4bvg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bvg RCSB], [http://www.ebi.ac.uk/pdbsum/4bvg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bvg ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/SIR3_HUMAN SIR3_HUMAN]] NAD-dependent protein deacetylase. Activates mitochondrial target proteins, including ACSS1, IDH2 and GDH by deacetylating key lysine residues. Contributes to the regulation of the cellular energy metabolism. Important for regulating tissue-specific ATP levels.<ref>PMID:16788062</ref> <ref>PMID:18680753</ref> <ref>PMID:18794531</ref> <ref>PMID:19535340</ref>  [[http://www.uniprot.org/uniprot/ACS2L_HUMAN ACS2L_HUMAN]] Important for maintaining normal body temperature during fasting and for energy homeostasis. Essential for energy expenditure under ketogenic conditions (By similarity). Converts acetate to acetyl-CoA so that it can be used for oxidation through the tricarboxylic cycle to produce ATP and CO(2).<ref>PMID:16788062</ref>
+[[https://www.uniprot.org/uniprot/SIR3_HUMAN SIR3_HUMAN]] NAD-dependent protein deacetylase. Activates mitochondrial target proteins, including ACSS1, IDH2 and GDH by deacetylating key lysine residues. Contributes to the regulation of the cellular energy metabolism. Important for regulating tissue-specific ATP levels.<ref>PMID:16788062</ref> <ref>PMID:18680753</ref> <ref>PMID:18794531</ref> <ref>PMID:19535340</ref>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-Sirtuins are protein deacetylases regulating metabolism and stress responses. The seven human Sirtuins (Sirt1-7) are attractive drug targets, but Sirtuin inhibition mechanisms are mostly unidentified. We report the molecular mechanism of Sirtuin inhibition by 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide (Ex-527). Inhibitor binding to potently inhibited Sirt1 and Thermotoga maritima Sir2 and to moderately inhibited Sirt3 requires NAD+, alone or together with acetylpeptide. Crystal structures of several Sirtuin inhibitor complexes show that Ex-527 occupies the nicotinamide site and a neighboring pocket and contacts the ribose of NAD+ or of the coproduct 2'-O-acetyl-ADP ribose. Complex structures with native alkylimidate and thio-analog support its catalytic relevance and show, together with biochemical assays, that only the coproduct complex is relevant for inhibition by Ex-527, which stabilizes the closed enzyme conformation preventing product release. Ex-527 inhibition thus exploits Sirtuin catalysis, and kinetic isoform differences explain its selectivity. Our results provide insights in Sirtuin catalysis and inhibition with important implications for drug development.
-Ex-527 inhibits Sirtuins by exploiting their unique NAD+-dependent deacetylation mechanism.,Gertz M, Fischer F, Nguyen GT, Lakshminarasimhan M, Schutkowski M, Weyand M, Steegborn C Proc Natl Acad Sci U S A. 2013 Jul 9. PMID:23840057<ref>PMID:23840057</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 4bvg" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 27: / Line 16: @@
 __TOC__
 </StructureSection>
-[[Category: Acetate--CoA ligase]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Gertz, M]]
+[[Category: Gertz M]]
-[[Category: Nguyen, G T.T]]
+[[Category: Nguyen GTT]]
-[[Category: Steegborn, C]]
+[[Category: Steegborn C]]
-[[Category: Weyand, M]]
+[[Category: Weyand M]]
-[[Category: Hydrolase-ligase complex]]
-[[Category: Nad-dependent deacetylase]]
-[[Category: Native intermediate]]