2vqj: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2vqj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VQJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2VQJ FirstGlance]. <br> | <table><tr><td colspan='2'>[[2vqj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VQJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2VQJ FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TFG:2,2,2-TRIFLUORO-1-{5-[(3-PHENYL-5,6-DIHYDROIMIDAZO[1,2-A]PYRAZIN-7(8H)-YL)CARBONYL]THIOPHEN-2-YL}ETHANE-1,1-DIOL'>TFG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TFG:2,2,2-TRIFLUORO-1-{5-[(3-PHENYL-5,6-DIHYDROIMIDAZO[1,2-A]PYRAZIN-7(8H)-YL)CARBONYL]THIOPHEN-2-YL}ETHANE-1,1-DIOL'>TFG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vqw|2vqw]], [[2vqq|2vqq]], [[2vqo|2vqo]], [[2vqv|2vqv]], [[2vqm|2vqm]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vqw|2vqw]], [[2vqq|2vqq]], [[2vqo|2vqo]], [[2vqv|2vqv]], [[2vqm|2vqm]]</td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vqj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2vqj RCSB], [http://www.ebi.ac.uk/pdbsum/2vqj PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vqj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2vqj RCSB], [http://www.ebi.ac.uk/pdbsum/2vqj PDBsum]</span></td></tr> | ||
<table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Bottomley, M J | [[Category: Bottomley, M J]] | ||
[[Category: Carfi, A | [[Category: Carfi, A]] | ||
[[Category: Cirillo, A | [[Category: Cirillo, A]] | ||
[[Category: Ferrigno, F | [[Category: Ferrigno, F]] | ||
[[Category: Francesco, R De | [[Category: Francesco, R De]] | ||
[[Category: Gallinari, P | [[Category: Gallinari, P]] | ||
[[Category: Giovine, P Di | [[Category: Giovine, P Di]] | ||
[[Category: Jones, P | [[Category: Jones, P]] | ||
[[Category: Neddermann, P | [[Category: Neddermann, P]] | ||
[[Category: Scarpelli, R | [[Category: Scarpelli, R]] | ||
[[Category: Steinkuhler, C | [[Category: Steinkuhler, C]] | ||
[[Category: Surdo, P Lo | [[Category: Surdo, P Lo]] | ||
[[Category: Chromatin]] | [[Category: Chromatin]] | ||
[[Category: Chromatin regulator]] | [[Category: Chromatin regulator]] | ||
Revision as of 19:10, 19 January 2015
STRUCTURE OF HDAC4 CATALYTIC DOMAIN BOUND TO A TRIFLUOROMETHYLKETONE INHBITORSTRUCTURE OF HDAC4 CATALYTIC DOMAIN BOUND TO A TRIFLUOROMETHYLKETONE INHBITOR
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHistone deacetylases (HDACs) regulate chromatin status and gene expression, and their inhibition is of significant therapeutic interest. To date, no biological substrate for class IIa HDACs has been identified, and only low activity on acetylated lysines has been demonstrated. Here, we describe inhibitor-bound and inhibitor-free structures of the histone deacetylase-4 catalytic domain (HDAC4cd) and of an HDAC4cd active site mutant with enhanced enzymatic activity toward acetylated lysines. The structures presented, coupled with activity data, provide the molecular basis for the intrinsically low enzymatic activity of class IIa HDACs toward acetylated lysines and reveal active site features that may guide the design of class-specific inhibitors. In addition, these structures reveal a conformationally flexible structural zinc-binding domain conserved in all class IIa enzymes. Importantly, either the mutation of residues coordinating the structural zinc ion or the binding of a class IIa selective inhibitor prevented the association of HDAC4 with the N-CoR.HDAC3 repressor complex. Together, these data suggest a key role of the structural zinc-binding domain in the regulation of class IIa HDAC functions. Structural and functional analysis of the human HDAC4 catalytic domain reveals a regulatory structural zinc-binding domain.,Bottomley MJ, Lo Surdo P, Di Giovine P, Cirillo A, Scarpelli R, Ferrigno F, Jones P, Neddermann P, De Francesco R, Steinkuhler C, Gallinari P, Carfi A J Biol Chem. 2008 Sep 26;283(39):26694-704. Epub 2008 Jul 8. PMID:18614528[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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