7o2p: Difference between revisions
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==Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 in complex with ITF3756== | ==Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 in complex with ITF3756== | ||
<StructureSection load='7o2p' size='340' side='right'caption='[[7o2p]]' scene=''> | <StructureSection load='7o2p' size='340' side='right'caption='[[7o2p]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7O2P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O2P FirstGlance]. <br> | <table><tr><td colspan='2'>[[7o2p]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7O2P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7O2P FirstGlance]. <br> | ||
</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=7o2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o2p OCA], [https://pdbe.org/7o2p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o2p RCSB], [https://www.ebi.ac.uk/pdbsum/7o2p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o2p ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=UZW:~{N}-oxidanyl-4-[(5-thiophen-2-yl-1,2,3,4-tetrazol-1-yl)methyl]benzamide'>UZW</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=7o2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7o2p OCA], [https://pdbe.org/7o2p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7o2p RCSB], [https://www.ebi.ac.uk/pdbsum/7o2p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7o2p ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Nonselective histone deacetylase (HDAC) inhibitors show dose-limiting side effects due to the inhibition of multiple, essential HDAC subtypes that can be limited or prevented by restricting their selectivity. We herein report the crystal structures of zebrafish HDAC6 catalytic domain 2 (zHDAC6-CD2) in complex with the selective HDAC6 inhibitors ITF3756 and ITF3985 and shed light on the role of fluorination in the selectivity of benzohydroxamate-based structures over class I isoforms. The reason for the enhancement in the selectivity of the benzohydroxamate-based compounds is the presence of specific interactions between the fluorinated linker and the key residues Gly582, Ser531, and His614 of zHDAC6, which are hindered in class I HDAC isoforms by the presence of an Aspartate that replaces Ser531. These results can be used in the design and development of novel, highly selective HDAC6 inhibitors. | |||
Role of Fluorination in the Histone Deacetylase 6 (HDAC6) Selectivity of Benzohydroxamate-Based Inhibitors.,Sandrone G, Cukier CD, Zrubek K, Marchini M, Vergani B, Caprini G, Fossati G, Steinkuhler C, Stevenazzi A ACS Med Chem Lett. 2021 Oct 11;12(11):1810-1817. doi:, 10.1021/acsmedchemlett.1c00425. eCollection 2021 Nov 11. PMID:34795871<ref>PMID:34795871</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7o2p" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Cukier | [[Category: Cukier, C D]] | ||
[[Category: Sandrone G]] | [[Category: Sandrone, G]] | ||
[[Category: Stevenazzi A]] | [[Category: Stevenazzi, A]] | ||
[[Category: Zrubek K]] | [[Category: Zrubek, K]] | ||
[[Category: Complex with hydroxamate inhibitor]] | |||
[[Category: Histone deacetylase]] | |||
[[Category: Hydrolase]] | |||