6uo5: Difference between revisions
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<StructureSection load='6uo5' size='340' side='right'caption='[[6uo5]], [[Resolution|resolution]] 1.44Å' scene=''> | <StructureSection load='6uo5' size='340' side='right'caption='[[6uo5]], [[Resolution|resolution]] 1.44Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6uo5]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UO5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UO5 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6uo5]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UO5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UO5 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=QCP:AR-42'>QCP</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=QCP:AR-42'>QCP</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">hdac6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</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=6uo5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uo5 OCA], [http://pdbe.org/6uo5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uo5 RCSB], [http://www.ebi.ac.uk/pdbsum/6uo5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uo5 ProSAT]</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=6uo5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uo5 OCA], [http://pdbe.org/6uo5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uo5 RCSB], [http://www.ebi.ac.uk/pdbsum/6uo5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uo5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Brachidanio rerio]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Christianson, D W]] | [[Category: Christianson, D W]] | ||
Revision as of 16:24, 18 December 2019
Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 1 (CD1) Y363F mutant complexed with AR-42Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 1 (CD1) Y363F mutant complexed with AR-42
Structural highlights
Publication Abstract from PubMedHistone deacetylase 6 (HDAC6) is emerging as a target for inhibition in therapeutic strategies aimed at treating cancer, neurodegenerative disease, and other disorders. Among the metal-dependent HDAC isozymes, HDAC6 is unique in that it contains two catalytic domains, CD1 and CD2. CD2 is a tubulin deacetylase and a tau deacetylase, and the development of HDAC6-selective inhibitors has focused exclusively on this domain. In contrast, there is a dearth of structural and functional information regarding CD1, which exhibits much narrower substrate specificity in comparison with CD2. As the first step in addressing the CD1 information gap, we now present X-ray crystal structures of seven inhibitor complexes with wild-type, Y363F, and K330L HDAC6 CD1. These structures broaden our understanding of molecular features that are important for catalysis and inhibitor binding. The active site of HDAC6 CD1 is wider than that of CD2, which is unexpected in view of the narrow substrate specificity of CD1. Amino acid substitutions between HDAC6 CD1 and CD2, as well as conformational differences in conserved residues, define striking differences in active site contours. Catalytic activity measurements with HDAC6 CD1 confirm the preference for peptide substrates containing C-terminal acetyllysine residues. However, these measurements also show that CD1 exhibits weak activity for peptide substrates bearing certain small amino acids on the carboxyl side of the scissile acetyllysine residue. Taken together, these results establish a foundation for understanding the structural basis of HDAC6 CD1 catalysis and inhibition, pointing to possible avenues for the development of HDAC6 CD1-selective inhibitors. Structural Basis of Catalysis and Inhibition of HDAC6 CD1, the Enigmatic Catalytic Domain of Histone Deacetylase 6.,Osko JD, Christianson DW Biochemistry. 2019 Dec 2. doi: 10.1021/acs.biochem.9b00934. PMID:31755702[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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