OCA at 11:40, 13 December 2023

OCA — Wed, 13 Dec 2023 11:40:47 GMT

←Older revision		Revision as of 11:40, 13 December 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8g1z is ~~ON HOLD until Paper~~ Publication	+	==Crystal Structure of Danio rerio histone deacetylase 6 catalytic domain 2 complexed with inhibitor Mz317==
		+	<StructureSection load='8g1z' size='340' side='right'caption='[[8g1z]], [[Resolution\|resolution]] 1.87Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8g1z]] 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=8G1Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8G1Z 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]] 1.87Å</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=YIZ:4-(acetamidomethyl)-N-hydroxybenzamide'>YIZ</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=8g1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8g1z OCA], [https://pdbe.org/8g1z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8g1z RCSB], [https://www.ebi.ac.uk/pdbsum/8g1z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8g1z ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/A7YT55_DANRE A7YT55_DANRE]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Dysregulation of both tubulin deacetylases sirtuin 2 (Sirt2) and the histone deacetylase 6 (HDAC6) has been associated with the pathogenesis of cancer and neurodegeneration, thus making these two enzymes promising targets for pharmaceutical intervention. Herein, we report the design, synthesis, and biological characterization of the first-in-class dual Sirt2/HDAC6 inhibitors as molecular tools for dual inhibition of tubulin deacetylation. Using biochemical in vitro assays and cell-based methods for target engagement, we identified Mz325 (33) as a potent and selective inhibitor of both target enzymes. Inhibition of both targets was further confirmed by X-ray crystal structures of Sirt2 and HDAC6 in complex with building blocks of 33. In ovarian cancer cells, 33 evoked enhanced effects on cell viability compared to single or combination treatment with the unconjugated Sirt2 and HDAC6 inhibitors. Thus, our dual Sirt2/HDAC6 inhibitors are important new tools to study the consequences and the therapeutic potential of dual inhibition of tubulin deacetylation.

-	~~Authors~~:	+	Development of First-in-Class Dual Sirt2/HDAC6 Inhibitors as Molecular Tools for Dual Inhibition of Tubulin Deacetylation.,Sinatra L, Vogelmann A, Friedrich F, Tararina MA, Neuwirt E, Colcerasa A, Konig P, Toy L, Yesiloglu TZ, Hilscher S, Gaitzsch L, Papenkordt N, Zhai S, Zhang L, Romier C, Einsle O, Sippl W, Schutkowski M, Gross O, Bendas G, Christianson DW, Hansen FK, Jung M, Schiedel M J Med Chem. 2023 Nov 9;66(21):14787-14814. doi: 10.1021/acs.jmedchem.3c01385. , Epub 2023 Oct 30. PMID:37902787<ref>PMID:37902787</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8g1z" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Danio rerio]]
		+	[[Category: Large Structures]]
		+	[[Category: Christianson DW]]
		+	[[Category: Tararina MA]]

OCA at 07:40, 15 March 2023

OCA — Wed, 15 Mar 2023 07:40:37 GMT

←Older revision		Revision as of 07:40, 15 March 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8g1z is ON HOLD	+	The entry 8g1z is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8g1z" [edit=sysop:move=sysop]

OCA — Wed, 15 Feb 2023 08:45:20 GMT

Protected "8g1z" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:45, 15 February 2023

OCA: New page: '''Unreleased structure''' The entry 8g1z is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 15 Feb 2023 08:45:19 GMT

New page: '''Unreleased structure''' The entry 8g1z is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8g1z is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

8g1z - Revision history

OCA at 11:40, 13 December 2023

OCA at 07:40, 15 March 2023

OCA: Protected "8g1z" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8g1z is ON HOLD Authors: Description: Category: Unreleased Structures