1c3s: Difference between revisions
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<StructureSection load='1c3s' size='340' side='right' caption='[[1c3s]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='1c3s' size='340' side='right' caption='[[1c3s]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1c3s]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[1c3s]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"aquifex_aeolicus"_huber_and_stetter_2001 "aquifex aeolicus" huber and stetter 2001]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C3S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1C3S FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SHH:OCTANEDIOIC+ACID+HYDROXYAMIDE+PHENYLAMIDE'>SHH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SHH:OCTANEDIOIC+ACID+HYDROXYAMIDE+PHENYLAMIDE'>SHH</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">[[1c3r|1c3r]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1c3r|1c3r]]</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=1c3s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c3s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1c3s RCSB], [http://www.ebi.ac.uk/pdbsum/1c3s 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=1c3s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c3s OCA], [http://pdbe.org/1c3s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1c3s RCSB], [http://www.ebi.ac.uk/pdbsum/1c3s PDBsum]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 1c3s" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Aquifex aeolicus]] | [[Category: Aquifex aeolicus huber and stetter 2001]] | ||
[[Category: Donigian, J R]] | [[Category: Donigian, J R]] | ||
[[Category: Finnin, M S]] | [[Category: Finnin, M S]] | ||
Revision as of 08:59, 11 September 2015
CRYSTAL STRUCTURE OF AN HDAC HOMOLOG COMPLEXED WITH SAHACRYSTAL STRUCTURE OF AN HDAC HOMOLOG COMPLEXED WITH SAHA
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) mediate changes in nucleosome conformation and are important in the regulation of gene expression. HDACs are involved in cell-cycle progression and differentiation, and their deregulation is associated with several cancers. HDAC inhibitors, such as trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), have anti-tumour effects, as they can inhibit cell growth, induce terminal differentiation and prevent the formation of tumours in mice models, and they are effective in the treatment of promyelocytic leukemia. Here we describe the structure of the histone deacetylase catalytic core, as revealed by the crystal structure of a homologue from the hyperthermophilic bacterium Aquifex aeolicus, that shares 35.2% identity with human HDAC1 over 375 residues, deacetylates histones in vitro and is inhibited by TSA and SAHA. The deacetylase, deacetylase-TSA and deacetylase-SAHA structures reveal an active site consisting of a tubular pocket, a zinc-binding site and two Asp-His charge-relay systems, and establish the mechanism of HDAC inhibition. The residues that make up the active site and contact the inhibitors are conserved across the HDAC family. These structures also suggest a mechanism for the deacetylation reaction and provide a framework for the further development of HDAC inhibitors as antitumour agents. Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors.,Finnin MS, Donigian JR, Cohen A, Richon VM, Rifkind RA, Marks PA, Breslow R, Pavletich NP Nature. 1999 Sep 9;401(6749):188-93. PMID:10490031[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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