OCA at 14:04, 18 October 2023

OCA — Wed, 18 Oct 2023 14:04:30 GMT

←Older revision		Revision as of 14:04, 18 October 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8cj7 is ~~ON HOLD until Paper~~ Publication	+	==HDAC6 selective degraded (difluoromethyl)-1,3,4-oxadiazole substrate inhibitor==
		+	<StructureSection load='8cj7' size='340' side='right'caption='[[8cj7]], [[Resolution\|resolution]] 1.51Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8cj7]] is a 3 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=8CJ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CJ7 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]] 1.51Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=UTO:6-[(5-pyridin-2-yl-1,2$l^{4},3,4-tetrazacyclopenta-1,3-dien-2-yl)methyl]pyridine-3-carbohydrazide'>UTO</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=8cj7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cj7 OCA], [https://pdbe.org/8cj7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cj7 RCSB], [https://www.ebi.ac.uk/pdbsum/8cj7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cj7 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 a unique member of the HDAC family mainly targeting cytosolic nonhistone substrates, such as alpha-tubulin, cortactin, and heat shock protein 90 to regulate cell proliferation, metastasis, invasion, and mitosis in tumors. We describe the identification and characterization of a series of 2-(difluoromethyl)-1,3,4-oxadiazoles (DFMOs) as selective nonhydroxamic acid HDAC6 inhibitors. By comparing structure-activity relationships and performing quantum mechanical calculations of the HDAC6 catalytic mechanism, we show that potent oxadiazoles are electrophilic substrates of HDAC6 and propose a mechanism for the bioactivation. We also observe that the inherent electrophilicity of the oxadiazoles makes them prone to degradation in water solution and the generation of potentially toxic products cannot be ruled out, limiting the developability for chronic diseases. However, the oxadiazoles demonstrate high oral bioavailability and low in vivo clearance and are excellent tools for studying the role of HDAC6 in vitro and in vivo in rats and mice.

-	~~Authors~~:	+	Selective and Bioavailable HDAC6 2-(Difluoromethyl)-1,3,4-oxadiazole Substrate Inhibitors and Modeling of Their Bioactivation Mechanism.,Ripa L, Sandmark J, Hughes G, Shamovsky I, Gunnarsson A, Johansson J, Llinas A, Collins M, Jung B, Noven A, Pemberton N, Mogemark M, Xiong Y, Li Q, Tangefjord S, Ek M, Astrand A J Med Chem. 2023 Oct 5. doi: 10.1021/acs.jmedchem.3c01269. PMID:37797307<ref>PMID:37797307</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8cj7" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Danio rerio]]
		+	[[Category: Large Structures]]
		+	[[Category: Ek M]]
		+	[[Category: Ripa L]]
		+	[[Category: Sandmark J]]

OCA at 05:33, 22 March 2023

OCA — Wed, 22 Mar 2023 05:33:53 GMT

←Older revision		Revision as of 05:33, 22 March 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8cj7 is ON HOLD	+	The entry 8cj7 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8cj7" [edit=sysop:move=sysop]

OCA — Wed, 22 Feb 2023 09:33:04 GMT

Protected "8cj7" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:33, 22 February 2023

OCA: New page: '''Unreleased structure''' The entry 8cj7 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 22 Feb 2023 09:33:00 GMT

New page: '''Unreleased structure''' The entry 8cj7 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8cj7 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

8cj7 - Revision history

OCA at 14:04, 18 October 2023

OCA at 05:33, 22 March 2023

OCA: Protected "8cj7" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8cj7 is ON HOLD Authors: Description: Category: Unreleased Structures