7c9n - Revision history

OCA at 16:00, 29 November 2023

OCA — Wed, 29 Nov 2023 16:00:54 GMT

←Older revision		Revision as of 16:00, 29 November 2023
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	<StructureSection load='7c9n' size='340' side='right'caption='[[7c9n]], [[Resolution\|resolution]] 2.47Å' scene=''>		<StructureSection load='7c9n' size='340' side='right'caption='[[7c9n]], [[Resolution\|resolution]] 2.47Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7c9n]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7C9N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C9N FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7c9n]] is a 2 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=7C9N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C9N FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FN9:3,5-dimethyl-2-[[(3R,5R)-1-methyl-5-phenyl-piperidin-3-yl]amino]pyrrolo[3,2-d]pyrimidin-4-one'>FN9</scene>~~</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]] 2.472Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SETDB1, ESET, KIAA0067, KMT1E ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FN9:3,5-dimethyl-2-[[(3R,5R)-1-methyl-5-phenyl-piperidin-3-yl]amino]pyrrolo[3,2-d]pyrimidin-4-one'>FN9</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=7c9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c9n OCA], [https://pdbe.org/7c9n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c9n RCSB], [https://www.ebi.ac.uk/pdbsum/7c9n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c9n ProSAT]</span></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=7c9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c9n OCA], [https://pdbe.org/7c9n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c9n RCSB], [https://www.ebi.ac.uk/pdbsum/7c9n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c9n ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/SETB1_HUMAN SETB1_HUMAN]] Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA methylation. Probably forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation. Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1. SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins.<ref>PMID:12869583</ref> <ref>PMID:14536086</ref> <ref>PMID:15327775</ref> <ref>PMID:17952062</ref>	+	[https://www.uniprot.org/uniprot/SETB1_HUMAN SETB1_HUMAN] Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA methylation. Probably forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation. Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1. SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins.<ref>PMID:12869583</ref> <ref>PMID:14536086</ref> <ref>PMID:15327775</ref> <ref>PMID:17952062</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 7c9n" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7c9n" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Histone methyltransferase 3D structures\|Histone methyltransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Guo, Y]]	+	[[Category: Guo Y]]
-	[[Category: Mao, X]]	+	[[Category: Mao X]]
-	[[Category: Xiong, L]]	+	[[Category: Xiong L]]
-	[[Category: Yang, S]]	+	[[Category: Yang S]]
-	~~[[Category: Gene regulation-inhibitor complex~~]]	+

OCA at 07:01, 14 April 2021

OCA — Wed, 14 Apr 2021 07:01:25 GMT

←Older revision		Revision as of 07:01, 14 April 2021
Line 1:		Line 1:

	==Crystal structure of SETDB1 tudor domain in complexed with Compound 1.==		==Crystal structure of SETDB1 tudor domain in complexed with Compound 1.==
-	<StructureSection load='7c9n' size='340' side='right'caption='[[7c9n]]' scene=''>	+	<StructureSection load='7c9n' size='340' side='right'caption='[[7c9n]], [[Resolution\|resolution]] 2.47Å' 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=7C9N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C9N FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7c9n]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7C9N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C9N 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=7c9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c9n OCA], [https://pdbe.org/7c9n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c9n RCSB], [https://www.ebi.ac.uk/pdbsum/7c9n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c9n ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FN9:3,5-dimethyl-2-[[(3R,5R)-1-methyl-5-phenyl-piperidin-3-yl]amino]pyrrolo[3,2-d]pyrimidin-4-one'>FN9</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SETDB1, ESET, KIAA0067, KMT1E ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=7c9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c9n OCA], [https://pdbe.org/7c9n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c9n RCSB], [https://www.ebi.ac.uk/pdbsum/7c9n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c9n ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/SETB1_HUMAN SETB1_HUMAN]] Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA methylation. Probably forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation. Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1. SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins.<ref>PMID:12869583</ref> <ref>PMID:14536086</ref> <ref>PMID:15327775</ref> <ref>PMID:17952062</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	SET domain bifurcated protein 1 (SETDB1) is a histone lysine methyltransferase that promotes the silencing of some tumour suppressor genes and is overexpressed in many cancers. SETDB1 contains a unique tandem tudor domain (TTD) that recognizes histone H3 sequences containing both methylated and acetylated lysines. Beginning with the identification of a hit compound (Cpd1), we discovered the first potent and selective small molecule SETDB1-TTD inhibitor (R,R)-59 through stepwise structure-guided optimization. (R,R)-59 showed a KD value of 0.088+/-0.045 muM in the ITC assay. The high potency of (R,R)-59 was well explained by the cocrystal structure of the (R,R)-59-TTD complex. (R,R)-59 is an endogenous binder competitive inhibitor. Evidence has also demonstrated its cellular target engagement. Interestingly, the enantiomer (S,S)-59 did not show activity in all the assays, highlighting the potential of (R,R)-59 as a tool compound in exploring the biological functions of SETDB1-TTD.
		+
		+	Structure-Guided Discovery of a Potent and Selective Cell-Active Inhibitor of SETDB1 Tudor Domain.,Guo Y, Mao X, Xiong L, Xia A, You J, Lin G, Wu C, Huang L, Wang Y, Yang S Angew Chem Int Ed Engl. 2021 Apr 12;60(16):8760-8765. doi:, 10.1002/anie.202017200. Epub 2021 Mar 8. PMID:33511756<ref>PMID:33511756</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7c9n" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Guo Y]]	+	[[Category: Guo, Y]]
-	[[Category: Mao X]]	+	[[Category: Mao, X]]
-	[[Category: Xiong L]]	+	[[Category: Xiong, L]]
-	[[Category: Yang S]]	+	[[Category: Yang, S]]
		+	[[Category: Gene regulation-inhibitor complex]]

OCA at 06:49, 7 April 2021

OCA — Wed, 07 Apr 2021 06:49:34 GMT

←Older revision		Revision as of 06:49, 7 April 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7c9n is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of SETDB1 tudor domain in complexed with Compound 1.==
-		+	<StructureSection load='7c9n' size='340' side='right'caption='[[7c9n]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7C9N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C9N FirstGlance]. <br>
-	~~Description~~:	+	</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=7c9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c9n OCA], [https://pdbe.org/7c9n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c9n RCSB], [https://www.ebi.ac.uk/pdbsum/7c9n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c9n ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Guo Y]]
		+	[[Category: Mao X]]
		+	[[Category: Xiong L]]
		+	[[Category: Yang S]]

OCA at 11:22, 8 July 2020

OCA — Wed, 08 Jul 2020 11:22:44 GMT

←Older revision		Revision as of 11:22, 8 July 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7c9n is ON HOLD	+	The entry 7c9n is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7c9n" [edit=sysop:move=sysop]

OCA — Wed, 17 Jun 2020 08:59:34 GMT

Protected "7c9n" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:59, 17 June 2020

OCA: New page: '''Unreleased structure''' The entry 7c9n is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 17 Jun 2020 08:59:33 GMT

New page: '''Unreleased structure''' The entry 7c9n is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7c9n is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]