5w5k
From Proteopedia
(Difference between revisions)
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==Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 in complex with KV70== | ==Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 in complex with KV70== | ||
- | <StructureSection load='5w5k' size='340' side='right' caption='[[5w5k]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='5w5k' size='340' side='right'caption='[[5w5k]], [[Resolution|resolution]] 2.70Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
- | <table><tr><td colspan='2'>[[5w5k]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W5K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W5K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5w5k]] is a 3 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=5W5K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W5K 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=K70:10-{[4-(hydroxycarbamoyl)phenyl]methyl}-5lambda~4~-pyrido[3,2-b][1,4]benzothiazin-10-ium'>K70</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=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=K70:10-{[4-(hydroxycarbamoyl)phenyl]methyl}-5lambda~4~-pyrido[3,2-b][1,4]benzothiazin-10-ium'>K70</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=5w5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w5k OCA], [http://pdbe.org/5w5k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w5k RCSB], [http://www.ebi.ac.uk/pdbsum/5w5k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w5k 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=5w5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w5k OCA], [http://pdbe.org/5w5k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w5k RCSB], [http://www.ebi.ac.uk/pdbsum/5w5k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w5k ProSAT]</span></td></tr> | ||
</table> | </table> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | The phenothiazine system was identified as a favorable cap group for potent and selective histone deacetylase 6 (HDAC6) inhibitors. Here, we report the preparation and systematic variation of phenothiazines and their analogues containing a benzhydroxamic acid moiety as the zinc-binding group. We evaluated their ability to selectively inhibit HDAC6 by a recombinant HDAC enzyme assay, by determining the protein acetylation levels in cells by western blotting (tubulin vs histone acetylation), and by assessing their effects on various cancer cell lines. Structure-activity relationship studies revealed that incorporation of a nitrogen atom into the phenothiazine framework results in increased potency and selectivity for HDAC6 (more than 500-fold selectivity relative to the inhibition of HDAC1, HDAC4, and HDAC8), as rationalized by molecular modeling and docking studies. The binding mode was confirmed by co-crystallization of the potent azaphenothiazine inhibitor with catalytic domain 2 from Danio rerio HDAC6. | ||
+ | |||
+ | Synthesis and Biological Investigation of Phenothiazine-Based Benzhydroxamic Acids as Selective Histone Deacetylase 6 Inhibitors.,Vogerl K, Ong N, Senger J, Herp D, Schmidtkunz K, Marek M, Muller M, Bartel K, Shaik TB, Porter NJ, Robaa D, Christianson DW, Romier C, Sippl W, Jung M, Bracher F J Med Chem. 2019 Feb 14;62(3):1138-1166. doi: 10.1021/acs.jmedchem.8b01090. Epub , 2019 Feb 1. PMID:30645113<ref>PMID:30645113</ref> | ||
+ | |||
+ | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
+ | </div> | ||
+ | <div class="pdbe-citations 5w5k" style="background-color:#fffaf0;"></div> | ||
+ | == References == | ||
+ | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
+ | [[Category: Brachidanio rerio]] | ||
+ | [[Category: Large Structures]] | ||
[[Category: Christianson, D W]] | [[Category: Christianson, D W]] | ||
[[Category: Porter, N J]] | [[Category: Porter, N J]] |
Revision as of 06:13, 10 July 2019
Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 in complex with KV70
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