5vsd - Revision history

OCA at 13:56, 4 October 2023

2023-10-04T13:56:55Z

← Older revision		Revision as of 13:56, 4 October 2023
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	<StructureSection load='5vsd' size='340' side='right'caption='[[5vsd]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='5vsd' size='340' side='right'caption='[[5vsd]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5vsd]] 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=5VSD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5VSD FirstGlance]. <br>		<table><tr><td colspan='2'>[[5vsd]] 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=5VSD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VSD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9HJ:6,7-dimethoxy-N~2~-methyl-N~4~-(1-methylpiperidin-4-yl)-N~2~-propylquinazoline-2,4-diamine'>9HJ</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 1.85Å</td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5vsf\|5vsf]], [[5vsc\|5vsc]], [[5vse\|5vse]]</td></tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9HJ:6,7-dimethoxy-N~2~-methyl-N~4~-(1-methylpiperidin-4-yl)-N~2~-propylquinazoline-2,4-diamine'>9HJ</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5vsd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vsd OCA], [https://pdbe.org/5vsd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vsd RCSB], [https://www.ebi.ac.uk/pdbsum/5vsd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vsd 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=5vsd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vsd OCA], [~~http~~://pdbe.org/5vsd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5vsd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5vsd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5vsd 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 ==
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	__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: Protein-small molecule inhibitor complex]]~~
	~~[[Category: Transferase-transferase inhibitor complex~~]]

OCA at 09:39, 1 January 2020

2020-01-01T09:39:21Z

← Older revision		Revision as of 09:39, 1 January 2020
Line 1:		Line 1:

	==Structure of human GLP SET-domain (EHMT1) in complex with inhibitor 13==		==Structure of human GLP SET-domain (EHMT1) in complex with inhibitor 13==
	<StructureSection load='5vsd' size='340' side='right' caption='[[5vsd]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='5vsd' size='340' side='right'caption='[[5vsd]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5vsd]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VSD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VSD FirstGlance]. <br>		<table><tr><td colspan='2'>[[5vsd]] 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=5VSD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VSD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9HJ:6,7-dimethoxy-N~2~-methyl-N~4~-(1-methylpiperidin-4-yl)-N~2~-propylquinazoline-2,4-diamine'>9HJ</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=9HJ:6,7-dimethoxy-N~2~-methyl-N~4~-(1-methylpiperidin-4-yl)-N~2~-propylquinazoline-2,4-diamine'>9HJ</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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">[[5vsf\|5vsf]], [[5vsc\|5vsc]], [[5vse\|5vse]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5vsf\|5vsf]], [[5vsc\|5vsc]], [[5vse\|5vse]]</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=5vsd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vsd OCA], [http://pdbe.org/5vsd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vsd RCSB], [http://www.ebi.ac.uk/pdbsum/5vsd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vsd 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=5vsd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vsd OCA], [http://pdbe.org/5vsd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vsd RCSB], [http://www.ebi.ac.uk/pdbsum/5vsd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vsd ProSAT]</span></td></tr>
	</table>		</table>
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	</div>		</div>
	<div class="pdbe-citations 5vsd" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5vsd" 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: Large Structures]]
	[[Category: Babault, N]]		[[Category: Babault, N]]
	[[Category: Jin, J]]		[[Category: Jin, J]]

OCA at 04:17, 4 August 2017

2017-08-04T04:17:06Z

← Older revision		Revision as of 04:17, 4 August 2017
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	~~The~~ entry ~~5vsd~~ is ~~ON HOLD~~		==Structure of human GLP SET-domain (EHMT1) in complex with inhibitor 13==
			<StructureSection load='5vsd' size='340' side='right' caption='[[5vsd]], [[Resolution\|resolution]] 1.85Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[5vsd]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VSD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VSD FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9HJ:6,7-dimethoxy-N~2~-methyl-N~4~-(1-methylpiperidin-4-yl)-N~2~-propylquinazoline-2,4-diamine'>9HJ</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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">[[5vsf\|5vsf]], [[5vsc\|5vsc]], [[5vse\|5vse]]</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=5vsd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vsd OCA], [http://pdbe.org/5vsd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vsd RCSB], [http://www.ebi.ac.uk/pdbsum/5vsd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vsd 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 ==
			Given the high homology between the protein lysine methyltransferases G9a-like protein (GLP) and G9a, it has been challenging to develop potent and selective inhibitors for either enzyme. Recently, we reported two quinazoline compounds, MS0124 and MS012, as GLP selective inhibitors. To further investigate the structure-activity relationships (SAR) of the quinazoline scaffold, we designed and synthesized a range of analogs bearing different 2-amino substitutions and evaluated their inhibition potencies against both GLP and G9a. These studies led to the identification of two new GLP selective inhibitors, 13 (MS3748) and 17 (MS3745), with 59- and 65-fold higher potency for GLP over G9a, which were confirmed by isothermal titration calorimetry (ITC). Crystal structures of GLP and G9a in complex with 13 and 17 provide insight into the interactions of the inhibitors with both proteins. In addition, we generated GLP selective inhibitors bearing a quinoline core instead of the quinazoline core.

	~~Authors:~~ Babault, N., ~~Xiong~~, Y., Liu, J., ~~Jin, J~~.		Structure-activity relationship studies of G9a-like protein (GLP) inhibitors.,Xiong Y, Li F, Babault N, Wu H, Dong A, Zeng H, Chen X, Arrowsmith CH, Brown PJ, Liu J, Vedadi M, Jin J Bioorg Med Chem. 2017 Aug 15;25(16):4414-4423. doi: 10.1016/j.bmc.2017.06.021., Epub 2017 Jun 19. PMID:28662962<ref>PMID:28662962</ref>

	~~Description: Structure~~ of ~~human GLP SET~~-~~domain (EHMT1) in complex with inhibitor 13~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[Category: Unreleased Structures]]~~		</div>
	~~[[Category: Xiong, Y]]~~		<div class="pdbe-citations 5vsd" style="background-color:#fffaf0;"></div>
			== References ==
			<references/>
			__TOC__
			</StructureSection>
	[[Category: Babault, N]]		[[Category: Babault, N]]
			[[Category: Jin, J]]
	[[Category: Liu, J]]		[[Category: Liu, J]]
	[[Category: ~~Jin~~, J]]		[[Category: Xiong, Y]]
			[[Category: Protein-small molecule inhibitor complex]]
			[[Category: Transferase-transferase inhibitor complex]]

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

2017-05-17T14:12:06Z

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

← Older revision	Revision as of 14:12, 17 May 2017
(No difference)

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

2017-05-17T14:12:04Z

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

New page

'''Unreleased structure'''

The entry 5vsd is ON HOLD

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

Description: Structure of human GLP SET-domain (EHMT1) in complex with inhibitor 13
[[Category: Unreleased Structures]]
[[Category: Xiong, Y]]
[[Category: Babault, N]]
[[Category: Liu, J]]
[[Category: Jin, J]]