6v7a: Difference between revisions
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==Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 (CD2) complexed with NF2657== | ==Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 (CD2) complexed with NF2657== | ||
<StructureSection load='6v7a' size='340' side='right'caption='[[6v7a]]' scene=''> | <StructureSection load='6v7a' size='340' side='right'caption='[[6v7a]], [[Resolution|resolution]] 2.09Å' 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=6V7A OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6v7a]] is a 1 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=6V7A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V7A FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.0874176Å</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=QQG:N-hydroxy-4-[(1-methyl-1,2-dihydro-1H-spiro[indole-3,4-piperidin]-1-yl)methyl]benzamide'>QQG</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=6v7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v7a OCA], [https://pdbe.org/6v7a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v7a RCSB], [https://www.ebi.ac.uk/pdbsum/6v7a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v7a ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/F8W4B7_DANRE F8W4B7_DANRE] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Histone deacetylase inhibitors (HDACi) have emerged as promising therapeutics for the treatment of neurodegeneration, cancer, and rare disorders. Herein, we report the development of a series of spiroindoline-based HDAC6 isoform-selective inhibitors based on the X-ray crystal studies of the hit 6a. We identified compound 6j as the most potent and selective hHDAC6 inhibitor of the series. Biological investigation of compounds 6b, 6h, and 6j demonstrated their antiproliferative activity against several cancer cell lines. Western blotting studies indicated that they were able to increase tubulin acetylation, without significant variation in histone acetylation state, and induced PARP cleavage indicating their apoptotic potential at the molecular level. 6j induced HDAC6-dependent pSTAT3 inhibition. | |||
Spiroindoline-Capped Selective HDAC6 Inhibitors: Design, Synthesis, Structural Analysis, and Biological Evaluation.,Saraswati AP, Relitti N, Brindisi M, Osko JD, Chemi G, Federico S, Grillo A, Brogi S, McCabe NH, Turkington RC, Ibrahim O, O'Sullivan J, Lamponi S, Ghanim M, Kelly VP, Zisterer D, Amet R, Hannon Barroeta P, Vanni F, Ulivieri C, Herp D, Sarno F, Di Costanzo A, Saccoccia F, Ruberti G, Jung M, Altucci L, Gemma S, Butini S, Christianson DW, Campiani G ACS Med Chem Lett. 2020 Sep 29;11(11):2268-2276. doi: , 10.1021/acsmedchemlett.0c00395. eCollection 2020 Nov 12. PMID:33214839<ref>PMID:33214839</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6v7a" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Danio rerio]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Christianson DW]] | [[Category: Christianson DW]] | ||
[[Category: Osko JD]] | [[Category: Osko JD]] | ||
Latest revision as of 08:05, 11 October 2023
Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 (CD2) complexed with NF2657
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