7buc - Revision history

OCA at 15:34, 29 November 2023

2023-11-29T15:34:12Z

←Older revision		Revision as of 15:34, 29 November 2023
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	<StructureSection load='7buc' size='340' side='right'caption='[[7buc]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='7buc' size='340' side='right'caption='[[7buc]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7buc]] 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=7BUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BUC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7buc]] 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=7BUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BUC FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F80:N2-[4-methoxy-3-(2,3,4,7-tetrahydro-1H-azepin-5-yl)phenyl]-N4,6-dimethyl-pyrimidine-2,4-diamine'>F80</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]] 2.6Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EHMT2, BAT8, C6orf30, G9A, KMT1C, NG36 ([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=F80:N2-[4-methoxy-3-(2,3,4,7-tetrahydro-1H-azepin-5-yl)phenyl]-N4,6-dimethyl-pyrimidine-2,4-diamine'>F80</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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=7buc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7buc OCA], [https://pdbe.org/7buc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7buc RCSB], [https://www.ebi.ac.uk/pdbsum/7buc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7buc 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=7buc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7buc OCA], [https://pdbe.org/7buc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7buc RCSB], [https://www.ebi.ac.uk/pdbsum/7buc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7buc ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/EHMT2_HUMAN EHMT2_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 mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. 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. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself.<ref>PMID:8457211</ref> <ref>PMID:11316813</ref> <ref>PMID:18438403</ref> <ref>PMID:20118233</ref> <ref>PMID:22387026</ref>	+	[https://www.uniprot.org/uniprot/EHMT2_HUMAN EHMT2_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 mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. 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. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself.<ref>PMID:8457211</ref> <ref>PMID:11316813</ref> <ref>PMID:18438403</ref> <ref>PMID:20118233</ref> <ref>PMID:22387026</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 7buc" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7buc" 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: Katayama, K]]	+	[[Category: Katayama K]]
-	[[Category: Mizuno, M]]	+	[[Category: Mizuno M]]
-	[[Category: Suzuki, M]]	+	[[Category: Suzuki M]]
-	~~[[Category: Protein-small molecule inhibitor complex]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 14:56, 17 June 2021

2021-06-17T14:56:34Z

←Older revision		Revision as of 14:56, 17 June 2021
Line 1:		Line 1:

	==Crystal structure of EHMT2 SET domain in complex with compound 13==		==Crystal structure of EHMT2 SET domain in complex with compound 13==
-	<StructureSection load='7buc' size='340' side='right'caption='[[7buc]]' scene=''>	+	<StructureSection load='7buc' size='340' side='right'caption='[[7buc]], [[Resolution\|resolution]] 2.60Å' 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=7BUC OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=7BUC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7buc]] 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=7BUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BUC FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=7buc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7buc OCA], [~~http~~://pdbe.org/7buc PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7buc RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7buc PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7buc 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=F80:N2-[4-methoxy-3-(2,3,4,7-tetrahydro-1H-azepin-5-yl)phenyl]-N4,6-dimethyl-pyrimidine-2,4-diamine'>F80</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">EHMT2, BAT8, C6orf30, G9A, KMT1C, NG36 ([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=7buc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7buc OCA], [https://pdbe.org/7buc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7buc RCSB], [https://www.ebi.ac.uk/pdbsum/7buc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7buc ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/EHMT2_HUMAN EHMT2_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 mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. 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. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself.<ref>PMID:8457211</ref> <ref>PMID:11316813</ref> <ref>PMID:18438403</ref> <ref>PMID:20118233</ref> <ref>PMID:22387026</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The discovery and optimization of a novel series of G9a/GLP (EHMT2/1) inhibitors are described. Starting from known G9a/GLP inhibitor 5, efforts to explore the structure-activity relationship and optimize drug properties led to a novel compound 13, the side chain of which was converted to tetrahydroazepine. Compound 13 showed increased G9a/GLP inhibitory activity compared with compound 5. In addition, compound 13 exhibited improved human ether-a-go-go related gene (hERG) inhibitory activity over compound 5 and also improved pharmacokinetic profile in mice (oral bioavailability: 17 to 40%). Finally, the co-crystal structure of G9a in complex with compound 13 provides the basis for the further development of tetrahydroazepine-based G9a/GLP inhibitors.
		+
		+	Discovery of novel histone lysine methyltransferase G9a/GLP (EHMT2/1) inhibitors: Design, synthesis, and structure-activity relationships of 2,4-diamino-6-methylpyrimidines.,Katayama K, Ishii K, Tsuda E, Yotsumoto K, Hiramoto K, Suzuki M, Yasumatsu I, Igarashi W, Torihata M, Ishiyama T, Katagiri T Bioorg Med Chem Lett. 2020 Oct 15;30(20):127475. doi: 10.1016/j.bmcl.2020.127475., Epub 2020 Aug 8. PMID:32781218<ref>PMID:32781218</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7buc" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Katayama K]]	+	[[Category: Katayama, K]]
-	[[Category: Mizuno M]]	+	[[Category: Mizuno, M]]
-	[[Category: Suzuki M]]	+	[[Category: Suzuki, M]]
		+	[[Category: Protein-small molecule inhibitor complex]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 08:02, 11 November 2020

2020-11-11T08:02:32Z

←Older revision		Revision as of 08:02, 11 November 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7buc ~~is ON HOLD until Apr 06 2022~~	+	==Crystal structure of EHMT2 SET domain in complex with compound 13==
-		+	<StructureSection load='7buc' size='340' side='right'caption='[[7buc]]' scene=''>
-	~~Authors~~: ~~Suzuki~~, M., ~~Mizuno~~, M., ~~Katayama~~, K.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BUC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7BUC FirstGlance]. <br>
-	~~Description: Crystal structure of EHMT2 SET domain in complex with compound 13~~	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7buc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7buc OCA], [http://pdbe.org/7buc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7buc RCSB], [http://www.ebi.ac.uk/pdbsum/7buc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7buc ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Katayama, K]]	+	__TOC__
-	[[Category: ~~Suzuki,~~ M]]	+	</StructureSection>
-	[[Category: ~~Mizuno,~~ M]]	+	[[Category: Large Structures]]
		+	[[Category: Katayama K]]
		+	[[Category: Mizuno M]]
		+	[[Category: Suzuki M]]

OCA at 05:23, 3 June 2020

2020-06-03T05:23:42Z

←Older revision		Revision as of 05:23, 3 June 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7buc is ON HOLD	+	The entry 7buc is ON HOLD until Apr 06 2022

	Authors: Suzuki, M., Mizuno, M., Katayama, K.		Authors: Suzuki, M., Mizuno, M., Katayama, K.
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	Description: Crystal structure of EHMT2 SET domain in complex with compound 13		Description: Crystal structure of EHMT2 SET domain in complex with compound 13
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: Katayama, K]]
	[[Category: Suzuki, M]]		[[Category: Suzuki, M]]
	[[Category: Mizuno, M]]		[[Category: Mizuno, M]]
-	[[Category: Katayama, K]]

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

2020-04-15T05:42:03Z

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

←Older revision

Revision as of 05:42, 15 April 2020

OCA: New page: '''Unreleased structure''' The entry 7buc is ON HOLD Authors: Suzuki, M., Mizuno, M., Katayama, K. Description: Crystal structure of EHMT2 SET domain in complex with compound 13 [[Cate...

2020-04-15T05:42:02Z

New page: '''Unreleased structure''' The entry 7buc is ON HOLD Authors: Suzuki, M., Mizuno, M., Katayama, K. Description: Crystal structure of EHMT2 SET domain in complex with compound 13 [[Cate...

New page

'''Unreleased structure'''

The entry 7buc is ON HOLD

Authors: Suzuki, M., Mizuno, M., Katayama, K.

Description: Crystal structure of EHMT2 SET domain in complex with compound 13
[[Category: Unreleased Structures]]
[[Category: Suzuki, M]]
[[Category: Mizuno, M]]
[[Category: Katayama, K]]