5tuz - Revision history

OCA at 13:13, 4 October 2023

OCA — Wed, 04 Oct 2023 13:13:00 GMT

←Older revision		Revision as of 13:13, 4 October 2023
Line 3:		Line 3:
	<StructureSection load='5tuz' size='340' side='right'caption='[[5tuz]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='5tuz' size='340' side='right'caption='[[5tuz]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5tuz]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TUZ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5TUZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5tuz]] 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=5TUZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TUZ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7L6:6,7-DIMETHOXY-N-(1-METHYLPIPERIDIN-4-YL)-2-(MORPHOLIN-4-YL)QUINAZOLIN-4-AMINE'>7L6</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.95Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5tuy\|5tuy]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7L6:6,7-DIMETHOXY-N-(1-METHYLPIPERIDIN-4-YL)-2-(MORPHOLIN-4-YL)QUINAZOLIN-4-AMINE'>7L6</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EHMT1, EUHMTASE1, GLP, KIAA1876, KMT1D ([http://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=5tuz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tuz OCA], [https://pdbe.org/5tuz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tuz RCSB], [https://www.ebi.ac.uk/pdbsum/5tuz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tuz ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5tuz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tuz OCA], [~~http~~://pdbe.org/5tuz PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5tuz RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5tuz PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5tuz ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/EHMT1_HUMAN EHMT1_HUMAN]] Defects in EHMT1 are the cause of chromosome 9q subtelomeric deletion syndrome (9q- syndrome) [MIM:[~~http~~://omim.org/entry/610253 610253]]. Common features seen in these patients are severe mental retardation, hypotonia, brachy(micro)cephaly, epileptic seizures, flat face with hypertelorism, synophrys, anteverted nares, cupid bow or tented upper lip, everted lower lip, prognathism, macroglossia, conotruncal heart defects, and behavioral problems.	+	[https://www.uniprot.org/uniprot/EHMT1_HUMAN EHMT1_HUMAN] Defects in EHMT1 are the cause of chromosome 9q subtelomeric deletion syndrome (9q- syndrome) [MIM:[https://omim.org/entry/610253 610253]. Common features seen in these patients are severe mental retardation, hypotonia, brachy(micro)cephaly, epileptic seizures, flat face with hypertelorism, synophrys, anteverted nares, cupid bow or tented upper lip, everted lower lip, prognathism, macroglossia, conotruncal heart defects, and behavioral problems.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/EHMT1_HUMAN EHMT1_HUMAN]] Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. During G0 phase, it probably contributes to silencing of MYC- and E2F-responsive genes, suggesting a role in G0/G1 transition in cell cycle. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53.<ref>PMID:12004135</ref> <ref>PMID:20118233</ref>	+	[https://www.uniprot.org/uniprot/EHMT1_HUMAN EHMT1_HUMAN] Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. During G0 phase, it probably contributes to silencing of MYC- and E2F-responsive genes, suggesting a role in G0/G1 transition in cell cycle. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53.<ref>PMID:12004135</ref> <ref>PMID:20118233</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 29:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Babault, N]]	+	[[Category: Babault N]]
-	[[Category: Jin, J]]	+	[[Category: Jin J]]
-	[[Category: Liu, J]]	+	[[Category: Liu J]]
-	[[Category: Xiong, Y]]	+	[[Category: Xiong Y]]
-	~~[[Category: Methyl transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 09:06, 1 January 2020

OCA — Wed, 01 Jan 2020 09:06:28 GMT

←Older revision		Revision as of 09:06, 1 January 2020
Line 1:		Line 1:

	==Structure of human GLP SET-domain (EHMT1) in complex with inhibitor MS0124==		==Structure of human GLP SET-domain (EHMT1) in complex with inhibitor MS0124==
-	<StructureSection load='5tuz' size='340' side='right' caption='[[5tuz]], [[Resolution\|resolution]] 1.95Å' scene=''>	+	<StructureSection load='5tuz' size='340' side='right'caption='[[5tuz]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5tuz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TUZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TUZ FirstGlance]. <br>		<table><tr><td colspan='2'>[[5tuz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TUZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TUZ FirstGlance]. <br>
Line 22:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 5tuz" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5tuz" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Histone methyltransferase 3D structures\|Histone methyltransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 27:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Babault, N]]		[[Category: Babault, N]]
	[[Category: Jin, J]]		[[Category: Jin, J]]

OCA at 14:27, 6 November 2017

OCA — Mon, 06 Nov 2017 14:27:49 GMT

←Older revision		Revision as of 14:27, 6 November 2017
Line 3:		Line 3:
	<StructureSection load='5tuz' size='340' side='right' caption='[[5tuz]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='5tuz' size='340' side='right' caption='[[5tuz]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5tuz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TUZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TUZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5tuz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TUZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TUZ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7L6:6,7-DIMETHOXY-N-(1-METHYLPIPERIDIN-4-YL)-2-(MORPHOLIN-4-YL)QUINAZOLIN-4-AMINE'>7L6</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7L6:6,7-DIMETHOXY-N-(1-METHYLPIPERIDIN-4-YL)-2-(MORPHOLIN-4-YL)QUINAZOLIN-4-AMINE'>7L6</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5tuy\|5tuy]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5tuy\|5tuy]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EHMT1, EUHMTASE1, GLP, KIAA1876, KMT1D ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5tuz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tuz OCA], [http://pdbe.org/5tuz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tuz RCSB], [http://www.ebi.ac.uk/pdbsum/5tuz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tuz ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5tuz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tuz OCA], [http://pdbe.org/5tuz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tuz RCSB], [http://www.ebi.ac.uk/pdbsum/5tuz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tuz ProSAT]</span></td></tr>
	</table>		</table>
Line 25:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Babault, N]]		[[Category: Babault, N]]
	[[Category: Jin, J]]		[[Category: Jin, J]]

OCA at 01:42, 11 March 2017

OCA — Sat, 11 Mar 2017 01:42:39 GMT

←Older revision		Revision as of 01:42, 11 March 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5tuz is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Structure of human GLP SET-domain (EHMT1) in complex with inhibitor MS0124==
		+	<StructureSection load='5tuz' size='340' side='right' caption='[[5tuz]], [[Resolution\|resolution]] 1.95Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5tuz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TUZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TUZ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7L6:6,7-DIMETHOXY-N-(1-METHYLPIPERIDIN-4-YL)-2-(MORPHOLIN-4-YL)QUINAZOLIN-4-AMINE'>7L6</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5tuy\|5tuy]]</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5tuz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tuz OCA], [http://pdbe.org/5tuz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tuz RCSB], [http://www.ebi.ac.uk/pdbsum/5tuz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tuz ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/EHMT1_HUMAN EHMT1_HUMAN]] Defects in EHMT1 are the cause of chromosome 9q subtelomeric deletion syndrome (9q- syndrome) [MIM:[http://omim.org/entry/610253 610253]]. Common features seen in these patients are severe mental retardation, hypotonia, brachy(micro)cephaly, epileptic seizures, flat face with hypertelorism, synophrys, anteverted nares, cupid bow or tented upper lip, everted lower lip, prognathism, macroglossia, conotruncal heart defects, and behavioral problems.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/EHMT1_HUMAN EHMT1_HUMAN]] Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. During G0 phase, it probably contributes to silencing of MYC- and E2F-responsive genes, suggesting a role in G0/G1 transition in cell cycle. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53.<ref>PMID:12004135</ref> <ref>PMID:20118233</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	G9a-like protein (GLP) and G9a are highly homologous protein lysine methyltransferases (PKMTs) sharing approximately 80% sequence identity in their catalytic domains. GLP and G9a form a heterodimer complex and catalyze mono- and dimethylation of histone H3 lysine 9 and nonhistone substrates. Although they are closely related, GLP and G9a possess distinct physiological and pathophysiological functions. Thus, GLP or G9a selective small-molecule inhibitors are useful tools to dissect their distinct biological functions. We previously reported potent and selective G9a/GLP dual inhibitors including UNC0638 and UNC0642. Here we report the discovery of potent and selective GLP inhibitors including 4 (MS0124) and 18 (MS012), which are >30-fold and 140-fold selective for GLP over G9a and other methyltransferases, respectively. The cocrystal structures of GLP and G9a in the complex with either 4 or 18 displayed virtually identical binding modes and interactions, highlighting the challenges in structure-based design of selective inhibitors for either enzyme.

-	~~Authors: Babault, N~~., Xiong, Y., ~~Liu~~, J., ~~Jin~~, J.	+	Discovery of Potent and Selective Inhibitors for G9a-Like Protein (GLP) Lysine Methyltransferase.,Xiong Y, Li F, Babault N, Dong A, Zeng H, Wu H, Chen X, Arrowsmith CH, Brown PJ, Liu J, Vedadi M, Jin J J Med Chem. 2017 Feb 14. doi: 10.1021/acs.jmedchem.6b01645. PMID:28135087<ref>PMID:28135087</ref>

-	~~Description: Structure~~ of ~~human GLP SET-domain (EHMT1) in complex with inhibitor MS0124~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
		+	<div class="pdbe-citations 5tuz" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Babault, N]]		[[Category: Babault, N]]
-	[[Category: Liu, J]]
	[[Category: Jin, J]]		[[Category: Jin, J]]
		+	[[Category: Liu, J]]
	[[Category: Xiong, Y]]		[[Category: Xiong, Y]]
		+	[[Category: Methyl transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA: Protected "5tuz" [edit=sysop:move=sysop]

OCA — Fri, 09 Dec 2016 17:55:17 GMT

Protected "5tuz" [edit=sysop:move=sysop]

←Older revision

Revision as of 17:55, 9 December 2016

OCA: New page: '''Unreleased structure''' The entry 5tuz is ON HOLD until Paper Publication Authors: Babault, N., Xiong, Y., Liu, J., Jin, J. Description: Structure of human GLP SET-domain (EHMT1) in...

OCA — Fri, 09 Dec 2016 17:55:16 GMT

New page: '''Unreleased structure''' The entry 5tuz is ON HOLD until Paper Publication Authors: Babault, N., Xiong, Y., Liu, J., Jin, J. Description: Structure of human GLP SET-domain (EHMT1) in...

New page

'''Unreleased structure'''

The entry 5tuz is ON HOLD until Paper Publication

Authors: Babault, N., Xiong, Y., Liu, J., Jin, J.

Description: Structure of human GLP SET-domain (EHMT1) in complex with inhibitor MS0124
[[Category: Unreleased Structures]]
[[Category: Babault, N]]
[[Category: Liu, J]]
[[Category: Jin, J]]
[[Category: Xiong, Y]]