OCA at 10:38, 22 May 2024

2024-05-22T10:38:14Z

←Older revision		Revision as of 10:38, 22 May 2024
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	==STRUCTURE OF HUMAN HDAC2 IN COMPLEX WITH AN ETHYL KETONE INHIBITOR CONTAINING A SPIRO-BICYCLIC GROUP (COMPOUND 22)==		==STRUCTURE OF HUMAN HDAC2 IN COMPLEX WITH AN ETHYL KETONE INHIBITOR CONTAINING A SPIRO-BICYCLIC GROUP (COMPOUND 22)==
-	<StructureSection load='7js8' size='340' side='right'caption='[[7js8]]' scene=''>	+	<StructureSection load='7js8' size='340' side='right'caption='[[7js8]], [[Resolution\|resolution]] 1.63Å' 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=7JS8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JS8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7js8]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JS8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JS8 FirstGlance]. <br>
-	</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=7js8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7js8 OCA], [https://pdbe.org/7js8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7js8 RCSB], [https://www.ebi.ac.uk/pdbsum/7js8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7js8 ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.634Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VJV:(1S)-N-{(1S)-7,7-dihydroxy-1-[4-(2-methylquinolin-6-yl)-1H-imidazol-2-yl]nonyl}-6-methyl-6-azaspiro[2.5]octane-1-carboxamide'>VJV</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=7js8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7js8 OCA], [https://pdbe.org/7js8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7js8 RCSB], [https://www.ebi.ac.uk/pdbsum/7js8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7js8 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/HDAC2_HUMAN HDAC2_HUMAN] Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR. Interacts in the late S-phase of DNA-replication with DNMT1 in the other transcriptional repressor complex composed of DNMT1, DMAP1, PCNA, CAF1. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development.<ref>PMID:19343227</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	We describe the discovery of histone deacetylase (HDACs) 1, 2, and 3 inhibitors with ethyl ketone as the zinc-binding group. These HDACs 1, 2, and 3 inhibitors have good enzymatic and cellular activity. Their serum shift in cellular potency has been minimized, and selectivity against hERG has been improved. They are also highly selective over HDACs 6 and 8. These inhibitors contain a variety of substituted heterocycles on the imidazole or oxazole scaffold. Compounds 31 and 48 stand out due to their good potency, high selectivity over HDACs 6 and 8, reduced hERG activity, optimized serum shift in cellular potency, and good rat and dog PK profiles.
		+
		+	Discovery of Ethyl Ketone-Based Highly Selective HDACs 1, 2, 3 Inhibitors for HIV Latency Reactivation with Minimum Cellular Potency Serum Shift and Reduced hERG Activity.,Yu W, Liu J, Clausen D, Yu Y, Duffy JL, Wang M, Xu S, Deng L, Suzuki T, Chung CC, Myers RW, Klein DJ, Fells JI, Holloway MK, Wu J, Wu G, Howell BJ, Barnard RJO, Kozlowski J J Med Chem. 2021 Apr 22;64(8):4709-4729. doi: 10.1021/acs.jmedchem.0c02150. Epub , 2021 Apr 2. PMID:33797924<ref>PMID:33797924</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7js8" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Histone deacetylase 3D structures\|Histone deacetylase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Klein DJ]]		[[Category: Klein DJ]]
	[[Category: Yu W]]		[[Category: Yu W]]

OCA at 06:06, 11 August 2021

2021-08-11T06:06:44Z

←Older revision		Revision as of 06:06, 11 August 2021
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-	'''Unreleased structure'''

-	~~The entry 7js8 is ON HOLD until Paper Publication~~	+	==STRUCTURE OF HUMAN HDAC2 IN COMPLEX WITH AN ETHYL KETONE INHIBITOR CONTAINING A SPIRO-BICYCLIC GROUP (COMPOUND 22)==
-		+	<StructureSection load='7js8' size='340' side='right'caption='[[7js8]]' scene=''>
-	~~Authors: Klein, D.J., Yu, W.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JS8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JS8 FirstGlance]. <br>
-	~~Description:~~ STRUCTURE OF HUMAN HDAC2 IN COMPLEX WITH AN ETHYL KETONE INHIBITOR CONTAINING A SPIRO-BICYCLIC GROUP (COMPOUND 22)	+	</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=7js8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7js8 OCA], [https://pdbe.org/7js8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7js8 RCSB], [https://www.ebi.ac.uk/pdbsum/7js8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7js8 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Klein~~, D.J~~]]	+	__TOC__
-	[[Category: Yu, W]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Klein DJ]]
		+	[[Category: Yu W]]

OCA at 09:03, 23 September 2020

2020-09-23T09:03:17Z

←Older revision		Revision as of 09:03, 23 September 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7js8 is ON HOLD	+	The entry 7js8 is ON HOLD until Paper Publication

	Authors: Klein, D.J., Yu, W.		Authors: Klein, D.J., Yu, W.

OCA: Protected "7js8" [edit=sysop:move=sysop]

2020-08-26T09:34:37Z

Protected "7js8" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:34, 26 August 2020

OCA: New page: '''Unreleased structure''' The entry 7js8 is ON HOLD Authors: Klein, D.J., Yu, W. Description: STRUCTURE OF HUMAN HDAC2 IN COMPLEX WITH AN ETHYL KETONE INHIBITOR CONTAINING A SPIRO-BIC...

2020-08-26T09:34:36Z

New page: '''Unreleased structure''' The entry 7js8 is ON HOLD Authors: Klein, D.J., Yu, W. Description: STRUCTURE OF HUMAN HDAC2 IN COMPLEX WITH AN ETHYL KETONE INHIBITOR CONTAINING A SPIRO-BIC...

New page

'''Unreleased structure'''

The entry 7js8 is ON HOLD

Authors: Klein, D.J., Yu, W.

Description: STRUCTURE OF HUMAN HDAC2 IN COMPLEX WITH AN ETHYL KETONE INHIBITOR CONTAINING A SPIRO-BICYCLIC GROUP (COMPOUND 22)
[[Category: Unreleased Structures]]
[[Category: Klein, D.J]]
[[Category: Yu, W]]

7js8 - Revision history

OCA at 10:38, 22 May 2024

OCA at 06:06, 11 August 2021

OCA at 09:03, 23 September 2020

OCA: Protected "7js8" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7js8 is ON HOLD Authors: Klein, D.J., Yu, W. Description: STRUCTURE OF HUMAN HDAC2 IN COMPLEX WITH AN ETHYL KETONE INHIBITOR CONTAINING A SPIRO-BIC...