7kxt - Revision history

OCA at 15:33, 18 October 2023

2023-10-18T15:33:52Z

←Older revision		Revision as of 15:33, 18 October 2023
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	<StructureSection load='7kxt' size='340' side='right'caption='[[7kxt]], [[Resolution\|resolution]] 2.15Å' scene=''>		<StructureSection load='7kxt' size='340' side='right'caption='[[7kxt]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7kxt]] 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=7KXT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KXT FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7kxt]] 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=7KXT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KXT FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene>, <scene name='pdbligand=XB7:1-[(4-fluorophenyl)methyl]-N-{1-[2-(4-methoxyphenyl)ethyl]piperidin-4-yl}-1H-benzimidazol-2-amine'>XB7</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]] 2.15Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EED ([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=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene>, <scene name='pdbligand=XB7:1-[(4-fluorophenyl)methyl]-N-{1-[2-(4-methoxyphenyl)ethyl]piperidin-4-yl}-1H-benzimidazol-2-amine'>XB7</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=7kxt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kxt OCA], [https://pdbe.org/7kxt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kxt RCSB], [https://www.ebi.ac.uk/pdbsum/7kxt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kxt 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=7kxt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kxt OCA], [https://pdbe.org/7kxt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kxt RCSB], [https://www.ebi.ac.uk/pdbsum/7kxt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kxt ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/EED_HUMAN EED_HUMAN]] Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Also recognizes 'Lys-26' trimethylated histone H1 with the effect of inhibiting PRC2 complex methyltransferase activity on nucleosomal histone H3 'Lys-27', whereas H3 'Lys-27' recognition has the opposite effect, enabling the propagation of this repressive mark. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1 and CDKN2A.<ref>PMID:9584199</ref> <ref>PMID:10581039</ref> <ref>PMID:14532106</ref> <ref>PMID:15385962</ref> <ref>PMID:15231737</ref> <ref>PMID:15225548</ref> <ref>PMID:16357870</ref> <ref>PMID:18285464</ref> <ref>PMID:20974918</ref>	+	[https://www.uniprot.org/uniprot/EED_HUMAN EED_HUMAN] Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Also recognizes 'Lys-26' trimethylated histone H1 with the effect of inhibiting PRC2 complex methyltransferase activity on nucleosomal histone H3 'Lys-27', whereas H3 'Lys-27' recognition has the opposite effect, enabling the propagation of this repressive mark. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1 and CDKN2A.<ref>PMID:9584199</ref> <ref>PMID:10581039</ref> <ref>PMID:14532106</ref> <ref>PMID:15385962</ref> <ref>PMID:15231737</ref> <ref>PMID:15225548</ref> <ref>PMID:16357870</ref> <ref>PMID:18285464</ref> <ref>PMID:20974918</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 7kxt" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7kxt" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Polycomb complex proteins 3D structures\|Polycomb complex proteins 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Arrowsmith~~, C H~~]]	+	[[Category: Arrowsmith CH]]
-	[[Category: Dong, A]]	+	[[Category: Dong A]]
-	[[Category: Du, D]]	+	[[Category: Du D]]
-	[[Category: Edwards~~, A M~~]]	+	[[Category: Edwards AM]]
-	[[Category: Liu, Y]]	+	[[Category: Liu Y]]
-	[[Category: Luo, C]]	+	[[Category: Luo C]]
-	[[Category: Min, J]]	+	[[Category: Min J]]
-	~~[[Category: Structural genomic~~]]	+	[[Category: Zhu L]]
-	[[Category: Zhu, L]]	+
-	~~[[Category: Eed]]~~	+
-	~~[[Category: Gene regulation]]~~	+
-	~~[[Category: Sgc]]~~	+
-	~~[[Category: Wd40~~]]	+

OCA at 10:34, 4 August 2021

2021-08-04T10:34:35Z

←Older revision		Revision as of 10:34, 4 August 2021
Line 1:		Line 1:

	==Crystal structure of human EED==		==Crystal structure of human EED==
-	<StructureSection load='7kxt' size='340' side='right'caption='[[7kxt]]' scene=''>	+	<StructureSection load='7kxt' size='340' side='right'caption='[[7kxt]], [[Resolution\|resolution]] 2.15Å' 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=7KXT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KXT FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7kxt]] 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=7KXT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KXT 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=7kxt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kxt OCA], [https://pdbe.org/7kxt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kxt RCSB], [https://www.ebi.ac.uk/pdbsum/7kxt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kxt 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=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene>, <scene name='pdbligand=XB7:1-[(4-fluorophenyl)methyl]-N-{1-[2-(4-methoxyphenyl)ethyl]piperidin-4-yl}-1H-benzimidazol-2-amine'>XB7</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EED ([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=7kxt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kxt OCA], [https://pdbe.org/7kxt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kxt RCSB], [https://www.ebi.ac.uk/pdbsum/7kxt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kxt ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/EED_HUMAN EED_HUMAN]] Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Also recognizes 'Lys-26' trimethylated histone H1 with the effect of inhibiting PRC2 complex methyltransferase activity on nucleosomal histone H3 'Lys-27', whereas H3 'Lys-27' recognition has the opposite effect, enabling the propagation of this repressive mark. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1 and CDKN2A.<ref>PMID:9584199</ref> <ref>PMID:10581039</ref> <ref>PMID:14532106</ref> <ref>PMID:15385962</ref> <ref>PMID:15231737</ref> <ref>PMID:15225548</ref> <ref>PMID:16357870</ref> <ref>PMID:18285464</ref> <ref>PMID:20974918</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Disruption of EZH2-embryonic ectoderm development (EED) protein-protein interaction (PPI) is a new promising cancer therapeutic strategy. We have previously reported the discovery of astemizole, a small-molecule inhibitor targeting the EZH2-EED PPI. Herein, we report the cocrystal structure of EED in complex with astemizole at 2.15 A. The structure elucidates the detailed binding mode of astemizole to EED and provides a structure-guided design for the discovery of a novel EZH2-EED interaction inhibitor, DC-PRC2in-01, with an affinity Kd of 4.56 muM. DC-PRC2in-01 destabilizes the PRC2 complex, thereby leading to the degradation of PRC2 core proteins and the decrease of global H3K27me3 levels in cancer cells. The proliferation of PRC2-driven lymphomas cells is effectively inhibited, and the cell cycle is arrested in the G0/G1 phase. Together, these data demonstrate that DC-PRC2in-01 could be an effective chemical probe for investigating the PRC2-related physiology and pathology and providing a promising chemical scaffold for further development.
		+
		+	Structure-Guided Development of Small-Molecule PRC2 Inhibitors Targeting EZH2-EED Interaction.,Du D, Xu D, Zhu L, Stazi G, Zwergel C, Liu Y, Luo Z, Li Y, Zhang Y, Zhu K, Ding Y, Liu J, Fan S, Zhao K, Zhang N, Kong X, Jiang H, Chen K, Zhao K, Valente S, Min J, Duan W, Luo C J Med Chem. 2021 Jun 24;64(12):8194-8207. doi: 10.1021/acs.jmedchem.0c02261. Epub, 2021 Jun 2. PMID:34077206<ref>PMID:34077206</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7kxt" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Arrowsmith CH]]	+	[[Category: Arrowsmith, C H]]
-	[[Category: Dong A]]	+	[[Category: Dong, A]]
-	[[Category: Du D]]	+	[[Category: Du, D]]
-	[[Category: Edwards AM]]	+	[[Category: Edwards, A M]]
-	[[Category: Liu Y]]	+	[[Category: Liu, Y]]
-	[[Category: Luo C]]	+	[[Category: Luo, C]]
-	[[Category: Min J]]	+	[[Category: Min, J]]
-	[[Category: Zhu L]]	+	[[Category: Structural genomic]]
		+	[[Category: Zhu, L]]
		+	[[Category: Eed]]
		+	[[Category: Gene regulation]]
		+	[[Category: Sgc]]
		+	[[Category: Wd40]]

OCA at 06:40, 24 February 2021

2021-02-24T06:40:55Z

←Older revision		Revision as of 06:40, 24 February 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7kxt ~~is ON HOLD~~	+	==Crystal structure of human EED==
-		+	<StructureSection load='7kxt' size='340' side='right'caption='[[7kxt]]' scene=''>
-	~~Authors~~: ~~Zhu, L~~.~~, Dong, A~~.~~, Du, D~~.~~, Liu, Y~~.~~, Luo, C~~., ~~Arrowsmith, C~~.H., ~~Edwards~~, A.M., ~~Min, J~~., ~~Structural Genomics Consortium (SGC)~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KXT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KXT FirstGlance]. <br>
-	~~Description: Crystal structure of human EED~~	+	</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=7kxt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kxt OCA], [https://pdbe.org/7kxt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kxt RCSB], [https://www.ebi.ac.uk/pdbsum/7kxt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kxt ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Arrowsmith~~, C.H]]~~	+	__TOC__
-	~~[[Category: Luo, C~~]]	+	</StructureSection>
-	[[Category: Dong, A]]	+	[[Category: Large Structures]]
-	[[Category: Du, D]]	+	[[Category: Arrowsmith CH]]
-	[[Category: ~~Min, J~~]]	+	[[Category: Dong A]]
-	[[Category: ~~Edwards, A.M~~]]	+	[[Category: Du D]]
-	[[Category: ~~Structural Genomics Consortium (Sgc)~~]]	+	[[Category: Edwards AM]]
-	[[Category: ~~Liu, Y~~]]	+	[[Category: Liu Y]]
-	[[Category: Zhu, L]]	+	[[Category: Luo C]]
		+	[[Category: Min J]]
		+	[[Category: Zhu L]]

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

2020-12-16T11:14:07Z

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

←Older revision

Revision as of 11:14, 16 December 2020

OCA: New page: '''Unreleased structure''' The entry 7kxt is ON HOLD Authors: Zhu, L., Dong, A., Du, D., Liu, Y., Luo, C., Arrowsmith, C.H., Edwards, A.M., Min, J., Structural Genomics Consortium (SGC)...

2020-12-16T11:14:06Z

New page: '''Unreleased structure''' The entry 7kxt is ON HOLD Authors: Zhu, L., Dong, A., Du, D., Liu, Y., Luo, C., Arrowsmith, C.H., Edwards, A.M., Min, J., Structural Genomics Consortium (SGC)...

New page

'''Unreleased structure'''

The entry 7kxt is ON HOLD

Authors: Zhu, L., Dong, A., Du, D., Liu, Y., Luo, C., Arrowsmith, C.H., Edwards, A.M., Min, J., Structural Genomics Consortium (SGC)

Description: Crystal structure of human EED
[[Category: Unreleased Structures]]
[[Category: Arrowsmith, C.H]]
[[Category: Luo, C]]
[[Category: Dong, A]]
[[Category: Du, D]]
[[Category: Min, J]]
[[Category: Edwards, A.M]]
[[Category: Structural Genomics Consortium (Sgc)]]
[[Category: Liu, Y]]
[[Category: Zhu, L]]