3c0z: Difference between revisions
New page: left|200px<br /><applet load="3c0z" size="350" color="white" frame="true" align="right" spinBox="true" caption="3c0z, resolution 2.10Å" /> '''Crystal structure of... |
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== | ==Crystal structure of catalytic domain of human histone deacetylase HDAC7 in complex with SAHA== | ||
<StructureSection load='3c0z' size='340' side='right'caption='[[3c0z]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3c0z]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2pqo 2pqo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C0Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C0Z FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> | |||
<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=SHH:OCTANEDIOIC+ACID+HYDROXYAMIDE+PHENYLAMIDE'>SHH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=3c0z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c0z OCA], [https://pdbe.org/3c0z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c0z RCSB], [https://www.ebi.ac.uk/pdbsum/3c0z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c0z ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/HDAC7_HUMAN HDAC7_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. Involved in muscle maturation by repressing transcription of myocyte enhancer factors such as MEF2A, MEF2B and MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors (By similarity). May be involved in Epstein-Barr virus (EBV) latency, possibly by repressing the viral BZLF1 gene.<ref>PMID:12239305</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c0/3c0z_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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=3c0z ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Histone deacetylases (HDACs) are protein deacetylases that play a role in repression of gene transcription and are emerging targets in cancer therapy. Here, we characterize the structure and enzymatic activity of the catalytic domain of human HDAC7 (cdHDAC7). Although HDAC7 normally exists as part of a multiprotein complex, we show that cdHDAC7 has a low level of deacetylase activity which can be inhibited by known HDAC inhibitors. The crystal structures of human cdHDAC7 and its complexes with two hydroxamate inhibitors are the first structures of the catalytic domain of class IIa HDACs and demonstrate significant differences with previously reported class I and class IIb-like HDAC structures. We show that cdHDAC7 has an additional class IIa HDAC-specific zinc binding motif adjacent to the active site which is likely to participate in substrate recognition and protein-protein interaction and may provide a site for modulation of activity. Furthermore, a different active site topology results in modified catalytic properties and in an enlarged active site pocket. Our studies provide mechanistic insights into class IIa HDACs and facilitate the design of specific modulators. | |||
Human HDAC7 harbors a class IIa histone deacetylase-specific zinc binding motif and cryptic deacetylase activity.,Schuetz A, Min J, Allali-Hassani A, Schapira M, Shuen M, Loppnau P, Mazitschek R, Kwiatkowski NP, Lewis TA, Maglathin RL, McLean TH, Bochkarev A, Plotnikov AN, Vedadi M, Arrowsmith CH J Biol Chem. 2008 Apr 25;283(17):11355-63. Epub 2008 Feb 19. PMID:18285338<ref>PMID:18285338</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3c0z" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Arrowsmith | [[Category: Arrowsmith CH]] | ||
[[Category: Bochkarev | [[Category: Bochkarev A]] | ||
[[Category: Edwards | [[Category: Edwards AM]] | ||
[[Category: Loppnau | [[Category: Loppnau P]] | ||
[[Category: Min | [[Category: Min J]] | ||
[[Category: Plotnikov | [[Category: Plotnikov AN]] | ||
[[Category: Schuetz A]] | |||
[[Category: Schuetz | [[Category: Sundstrom M]] | ||
[[Category: Sundstrom | [[Category: Weigelt J]] | ||
[[Category: Weigelt | |||
