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3rqd

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Ideal Thiolate-Zinc Coordination Geometry in Depsipeptide Binding to Histone Deacetylase 8

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 ==Ideal Thiolate-Zinc Coordination Geometry in Depsipeptide Binding to Histone Deacetylase 8==
-<StructureSection load='3rqd' size='340' side='right' caption='[[3rqd]], [[Resolution|resolution]] 2.14&Aring;' scene=''>
+<StructureSection load='3rqd' size='340' side='right'caption='[[3rqd]], [[Resolution|resolution]] 2.14&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3rqd]] is a 4 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=3RQD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RQD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3rqd]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Symploca Symploca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RQD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RQD FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.143&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=02G:(3S,4E)-3-HYDROXY-7-SULFANYLHEPT-4-ENOIC+ACID'>02G</scene>, <scene name='pdbligand=03Y:2-METHYL-L-CYSTEINE'>03Y</scene>, <scene name='pdbligand=BB9:(2Z)-2-AMINO-3-SULFANYLPROP-2-ENOIC+ACID'>BB9</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=02G:(3S,4E)-3-HYDROXY-7-SULFANYLHEPT-4-ENOIC+ACID'>02G</scene>, <scene name='pdbligand=03Y:2-METHYL-L-CYSTEINE'>03Y</scene>, <scene name='pdbligand=BB9:(2Z)-2-AMINO-3-SULFANYLPROP-2-ENOIC+ACID'>BB9</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HDAC8, HDACL1, CDA07 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3rqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rqd OCA], [https://pdbe.org/3rqd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rqd RCSB], [https://www.ebi.ac.uk/pdbsum/3rqd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rqd 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/Histone_deacetylase Histone deacetylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.98 3.5.1.98] </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=3rqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rqd OCA], [http://pdbe.org/3rqd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3rqd RCSB], [http://www.ebi.ac.uk/pdbsum/3rqd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3rqd ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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>
+[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>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-Largazole is a macrocyclic depsipeptide originally isolated from the marine cyanobacterium Symploca sp., which is indigenous to the warm, blue-green waters of Key Largo, Florida (whence largazole derives its name). Largazole contains an unusual thiazoline-thiazole ring system that rigidifies its macrocyclic skeleton, and it also contains a lipophilic thioester side chain. Hydrolysis of the thioester in vivo yields largazole thiol, which exhibits remarkable antiproliferative effects and is believed to be the most potent inhibitor of the metal-dependent histone deacetylases (HDACs). Here, the 2.14 A-resolution crystal structure of the HDAC8-largazole thiol complex is the first of an HDAC complexed with a macrocyclic inhibitor and reveals that ideal thiolate-zinc coordination geometry is the key chemical feature responsible for its exceptional affinity and biological activity. Notably, the core structure of largazole is conserved in romidepsin, a depsipeptide natural product formulated as the drug Istodax recently approved for cancer chemotherapy. Accordingly, the structure of the HDAC8-largazole thiol complex is the first to illustrate the mode of action of a new class of therapeutically important HDAC inhibitors.
-Structural basis of the antiproliferative activity of largazole, a depsipeptide inhibitor of the histone deacetylases.,Cole KE, Dowling DP, Boone MA, Phillips AJ, Christianson DW J Am Chem Soc. 2011 Aug 17;133(32):12474-7. Epub 2011 Jul 26. PMID:21790156<ref>PMID:21790156</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 3rqd" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Histone deacetylase|Histone deacetylase]]
+*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Histone deacetylase]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
+[[Category: Large Structures]]
-[[Category: Christianson, D W]]
+[[Category: Symploca]]
-[[Category: Cole, K E]]
+[[Category: Christianson DW]]
-[[Category: Dowling, D P]]
+[[Category: Cole KE]]
-[[Category: Histone deacetylation]]
+[[Category: Dowling DP]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: Largazole]]

3rqd

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Ideal Thiolate-Zinc Coordination Geometry in Depsipeptide Binding to Histone Deacetylase 8

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