5g0i: Difference between revisions
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==Crystal structure of Danio rerio HDAC6 CD1 and CD2 (linker cleaved) in complex with Nexturastat A== | ==Crystal structure of Danio rerio HDAC6 CD1 and CD2 (linker cleaved) in complex with Nexturastat A== | ||
<StructureSection load='5g0i' size='340' side='right' caption='[[5g0i]], [[Resolution|resolution]] 1.99Å' scene=''> | <StructureSection load='5g0i' size='340' side='right'caption='[[5g0i]], [[Resolution|resolution]] 1.99Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5g0i]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5G0I OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[5g0i]] is a 2 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=5G0I OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5G0I FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=N4R:NEXTURASTAT+A'>N4R</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" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=N4R:NEXTURASTAT+A'>N4R</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">[[5g0f|5g0f]], [[5g0g|5g0g]], [[5g0h|5g0h]], [[5g0j|5g0j]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5g0f|5g0f]], [[5g0g|5g0g]], [[5g0h|5g0h]], [[5g0j|5g0j]]</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5g0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g0i OCA], [http://pdbe.org/5g0i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5g0i RCSB], [http://www.ebi.ac.uk/pdbsum/5g0i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5g0i ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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</div> | </div> | ||
<div class="pdbe-citations 5g0i" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5g0i" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Brachidanio rerio]] | |||
[[Category: Large Structures]] | |||
[[Category: Gut, H]] | [[Category: Gut, H]] | ||
[[Category: Helquist, P]] | [[Category: Helquist, P]] | ||
Revision as of 09:33, 13 May 2020
Crystal structure of Danio rerio HDAC6 CD1 and CD2 (linker cleaved) in complex with Nexturastat ACrystal structure of Danio rerio HDAC6 CD1 and CD2 (linker cleaved) in complex with Nexturastat A
Structural highlights
Publication Abstract from PubMedWe report crystal structures of zebrafish histone deacetylase 6 (HDAC6) catalytic domains in tandem or as single domains in complex with the (R) and (S) enantiomers of trichostatin A (TSA) or with the HDAC6-specific inhibitor nexturastat A. The tandem domains formed, together with the inter-domain linker, an ellipsoid-shaped complex with pseudo-twofold symmetry. We identified important active site differences between both catalytic domains and revealed the binding mode of HDAC6 selective inhibitors. HDAC inhibition assays with (R)- and (S)-TSA showed that (R)-TSA was a broad-range inhibitor, whereas (S)-TSA had moderate selectivity for HDAC6. We identified a uniquely positioned alpha-helix and a flexible tryptophan residue in the loop joining alpha-helices H20 to H21 as critical for deacetylation of the physiologic substrate tubulin. Using single-molecule measurements and biochemical assays we demonstrated that HDAC6 catalytic domain 2 deacetylated alpha-tubulin lysine 40 in the lumen of microtubules, but that its preferred substrate was unpolymerized tubulin. Structural insights into HDAC6 tubulin deacetylation and its selective inhibition.,Miyake Y, Keusch JJ, Wang L, Saito M, Hess D, Wang X, Melancon BJ, Helquist P, Gut H, Matthias P Nat Chem Biol. 2016 Jul 25. doi: 10.1038/nchembio.2140. PMID:27454931[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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