6pye: Difference between revisions
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New page: '''Unreleased structure''' The entry 6pye is ON HOLD Authors: Description: Category: Unreleased Structures |
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==Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 complexed with NR160== | |||
<StructureSection load='6pye' size='340' side='right'caption='[[6pye]], [[Resolution|resolution]] 1.48Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6pye]] 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=6PYE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PYE FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.480003Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=P5Y:N-[(1-benzyl-1H-tetrazol-5-yl)methyl]-N-{[4-(hydroxycarbamoyl)phenyl]methyl}-2-(trifluoromethyl)benzamide'>P5Y</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=6pye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pye OCA], [https://pdbe.org/6pye PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pye RCSB], [https://www.ebi.ac.uk/pdbsum/6pye PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pye 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 emerging target for the treatment of cancer, neurodegenerative diseases, inflammation, and other diseases. Here, we present the multicomponent synthesis and structure-activity relationship of a series of tetrazole-based HDAC6 inhibitors. We discovered the hit compound NR-160 by investigating the inhibition of recombinant HDAC enzymes and protein acetylation. A cocrystal structure of HDAC6 complexed with NR-160 disclosed that the steric complementarity of the bifurcated capping group of NR-160 to the L1 and L2 loop pockets may be responsible for its HDAC6-selective inhibition. While NR-160 displayed only low cytotoxicity as a single agent against leukemia cell lines, it augmented the apoptosis induction of the proteasome inhibitor bortezomib in combination experiments significantly. Furthermore, a combinatorial high-throughput drug screen revealed significantly enhanced cytotoxicity when NR-160 was used in combination with epirubicin and daunorubicin. The synergistic effect in combination with bortezomib and anthracyclines highlights the potential of NR-160 in combination therapies. | |||
Multicomponent Synthesis, Binding Mode, and Structure-Activity Relationship of Selective Histone Deacetylase 6 (HDAC6) Inhibitors with Bifurcated Capping Groups.,Ressing N, Sonnichsen M, Osko JD, Scholer A, Schliehe-Diecks J, Skerhut A, Borkhardt A, Hauer J, Kassack MU, Christianson DW, Bhatia S, Hansen FK J Med Chem. 2020 Sep 24;63(18):10339-10351. doi: 10.1021/acs.jmedchem.9b01888., Epub 2020 Sep 1. PMID:32803970<ref>PMID:32803970</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6pye" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Histone deacetylase 3D structures|Histone deacetylase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Danio rerio]] | |||
[[Category: Large Structures]] | |||
[[Category: Christianson DW]] | |||
[[Category: Osko JD]] | |||
Latest revision as of 07:38, 11 October 2023
Crystal structure of Danio rerio histone deacetylase 6 catalytic domain 2 complexed with NR160
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