1w22

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{{Seed}}
 
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[[Image:1w22.png|left|200px]]
 
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==Crystal structure of inhibited human HDAC8==
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The line below this paragraph, containing "STRUCTURE_1w22", creates the "Structure Box" on the page.
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<StructureSection load='1w22' size='340' side='right'caption='[[1w22]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1w22]] 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=1W22 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W22 FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NHB:N-HYDROXY-4-(METHYL{[5-(2-PYRIDINYL)-2-THIENYL]SULFONYL}AMINO)BENZAMIDE'>NHB</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_1w22| PDB=1w22 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1w22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w22 OCA], [https://pdbe.org/1w22 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w22 RCSB], [https://www.ebi.ac.uk/pdbsum/1w22 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w22 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/HDAC8_HUMAN HDAC8_HUMAN] Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. May play a role in smooth muscle cell contractility.<ref>PMID:10748112</ref> <ref>PMID:10926844</ref> <ref>PMID:10922473</ref> <ref>PMID:14701748</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w2/1w22_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1w22 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Histone deacetylases (HDACs) are a family of enzymes involved in the regulation of gene expression, DNA repair, and stress response. These processes often are altered in tumors, and HDAC inhibitors have had pronounced antitumor activity with promising results in clinical trials. Here, we report the crystal structure of human HDAC8 in complex with a hydroxamic acid inhibitor. Such a structure of a eukaryotic zinc-dependent HDAC has not be described previously. Similar to bacterial HDAC-like protein, HDAC8 folds in a single alpha/beta domain. The inhibitor and the zinc-binding sites are similar in both proteins. However, significant differences are observed in the length and structure of the loops surrounding the active site, including the presence of two potassium ions in HDAC8 structure, one of which interacts with key catalytic residues. CD data suggest a direct role of potassium in the fold stabilization of HDAC8. Knockdown of HDAC8 by RNA interference inhibits growth of human lung, colon, and cervical cancer cell lines, highlighting the importance of this HDAC subtype for tumor cell proliferation. Our findings open the way for the design and development of selective inhibitors of HDAC8 as possible antitumor agents.
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===CRYSTAL STRUCTURE OF INHIBITED HUMAN HDAC8===
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Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor.,Vannini A, Volpari C, Filocamo G, Casavola EC, Brunetti M, Renzoni D, Chakravarty P, Paolini C, De Francesco R, Gallinari P, Steinkuhler C, Di Marco S Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15064-9. Epub 2004 Oct 11. PMID:15477595<ref>PMID:15477595</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1w22" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_15477595}}, adds the Publication Abstract to the page
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*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 15477595 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_15477595}}
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__TOC__
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</StructureSection>
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==About this Structure==
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1W22 is a 2 chains structure of sequences 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=1W22 OCA].
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==Reference==
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<ref group="xtra">PMID:15477595</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Casavola, E Caroli.]]
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[[Category: Large Structures]]
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[[Category: Marco, S Di.]]
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[[Category: Caroli Casavola E]]
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[[Category: Vannini, A.]]
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[[Category: Di Marco S]]
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[[Category: Volpari, C.]]
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[[Category: Vannini A]]
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[[Category: Chromatin]]
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[[Category: Volpari C]]
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[[Category: Deacetylation]]
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[[Category: Hdac]]
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[[Category: Hdac8]]
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[[Category: Histone deacetylase]]
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[[Category: Hydrolase]]
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[[Category: Hydroxamic acid]]
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[[Category: Nuclear protein]]
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[[Category: Repressor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 03:12:11 2009''
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Current revision

Crystal structure of inhibited human HDAC8

PDB ID 1w22

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