8a8z: Difference between revisions

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 == Structural highlights ==
 <table><tr><td colspan='2'>[[8a8z]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8A8Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A8Z FirstGlance]. <br>
-</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=LDL:4-[[4-[4-(imidazolidin-2-ylideneamino)phenyl]-1,2,3-triazol-1-yl]methyl]benzohydrazide'>LDL</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]] 1.6&#8491;</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=LDL:4-[[4-[4-(imidazolidin-2-ylideneamino)phenyl]-1,2,3-triazol-1-yl]methyl]benzohydrazide'>LDL</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=8a8z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a8z OCA], [https://pdbe.org/8a8z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a8z RCSB], [https://www.ebi.ac.uk/pdbsum/8a8z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a8z ProSAT]</span></td></tr>
 </table>
 == Function ==
 [https://www.uniprot.org/uniprot/F8W4B7_DANRE F8W4B7_DANRE]
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-Histone deacetylase 6 (HDAC6) is an attractive drug development target because of its role in the immune response, neuropathy, and cancer. Knockout mice develop normally and have no apparent phenotype, suggesting that selective inhibitors should have an excellent therapeutic window. Unfortunately, current HDAC6 inhibitors have only moderate selectivity and may inhibit other HDAC subtypes at high concentrations, potentially leading to side effects. Recently, substituted oxadiazoles have attracted attention as a promising novel HDAC inhibitor chemotype, but their mechanism of action is unknown. Here, we show that compounds containing a difluoromethyl-1,3,4-oxadiazole (DFMO) moiety are potent and single-digit nanomolar inhibitors with an unprecedented greater than 10(4)-fold selectivity for HDAC6 over all other HDAC subtypes. By combining kinetics, X-ray crystallography, and mass spectrometry, we found that DFMO derivatives are slow-binding substrate analogs of HDAC6 that undergo an enzyme-catalyzed ring opening reaction, forming a tight and long-lived enzyme-inhibitor complex. The elucidation of the mechanism of action of DFMO derivatives paves the way for the rational design of highly selective inhibitors of HDAC6 and possibly of other HDAC subtypes as well with potentially important therapeutic implications.
-Difluoromethyl-1,3,4-oxadiazoles are slow-binding substrate analog inhibitors of histone deacetylase 6 with unprecedented isotype selectivity.,Cellupica E, Caprini G, Cordella P, Cukier C, Fossati G, Marchini M, Rocchio I, Sandrone G, Vanoni MA, Vergani B, Zrubek K, Stevenazzi A, Steinkuhler C J Biol Chem. 2022 Dec 15;299(1):102800. doi: 10.1016/j.jbc.2022.102800. PMID:36528061<ref>PMID:36528061</ref>
+==See Also==
+*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]]
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 8a8z" style="background-color:#fffaf0;"></div>
-== References ==
-<references/>
 __TOC__
 </StructureSection>