5u8f - Revision history

OCA at 13:22, 4 October 2023

OCA — Wed, 04 Oct 2023 13:22:56 GMT

←Older revision		Revision as of 13:22, 4 October 2023
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	<StructureSection load='5u8f' size='340' side='right'caption='[[5u8f]], [[Resolution\|resolution]] 1.34Å' scene=''>		<StructureSection load='5u8f' size='340' side='right'caption='[[5u8f]], [[Resolution\|resolution]] 1.34Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5u8f]] is a 1 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=5U8F OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5U8F FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5u8f]] is a 1 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=5U8F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U8F FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=82G:(3R,4S)-1-[(1S)-7-FLUORO-2,3-DIHYDRO-1H-INDEN-1-YL]-N,N-DIMETHYL-4-(1-METHYL-1H-INDOL-3-YL)PYRROLIDIN-3-AMINE'>82G</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]] 1.343Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5u8a\|5u8a]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=82G:(3R,4S)-1-[(1S)-7-FLUORO-2,3-DIHYDRO-1H-INDEN-1-YL]-N,N-DIMETHYL-4-(1-METHYL-1H-INDOL-3-YL)PYRROLIDIN-3-AMINE'>82G</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EED ([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=5u8f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u8f OCA], [https://pdbe.org/5u8f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u8f RCSB], [https://www.ebi.ac.uk/pdbsum/5u8f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u8f ProSAT]</span></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=5u8f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u8f OCA], [~~http~~://pdbe.org/5u8f PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5u8f RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5u8f PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5u8f ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://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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	==See Also==		==See Also==
-	*[[Polycomb\|Polycomb]]	+	*[[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: Jakob~~, C G~~]]	+	[[Category: Jakob CG]]
-	[[Category: Zhu, H]]	+	[[Category: Zhu H]]
-	~~[[Category: Protein binding-inhibitor complex]]~~	+
-	~~[[Category: Wd40 prc2~~]]	+

OCA at 12:29, 23 September 2020

OCA — Wed, 23 Sep 2020 12:29:21 GMT

←Older revision		Revision as of 12:29, 23 September 2020
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	==Polycomb protein EED in complex with inhibitor: (3R,4S)-1-[(1S)-7-fluoro-2,3-dihydro-1H-inden-1-yl]-N,N-dimethyl-4-(1-methyl-1H-indol-3-yl)pyrrolidin-3-amine==		==Polycomb protein EED in complex with inhibitor: (3R,4S)-1-[(1S)-7-fluoro-2,3-dihydro-1H-inden-1-yl]-N,N-dimethyl-4-(1-methyl-1H-indol-3-yl)pyrrolidin-3-amine==
-	<StructureSection load='5u8f' size='340' side='right' caption='[[5u8f]], [[Resolution\|resolution]] 1.34Å' scene=''>	+	<StructureSection load='5u8f' size='340' side='right'caption='[[5u8f]], [[Resolution\|resolution]] 1.34Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5u8f]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U8F OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5U8F FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5u8f]] is a 1 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=5U8F OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5U8F FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=82G:(3R,4S)-1-[(1S)-7-FLUORO-2,3-DIHYDRO-1H-INDEN-1-YL]-N,N-DIMETHYL-4-(1-METHYL-1H-INDOL-3-YL)PYRROLIDIN-3-AMINE'>82G</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=82G:(3R,4S)-1-[(1S)-7-FLUORO-2,3-DIHYDRO-1H-INDEN-1-YL]-N,N-DIMETHYL-4-(1-METHYL-1H-INDOL-3-YL)PYRROLIDIN-3-AMINE'>82G</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5u8a\|5u8a]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5u8a\|5u8a]]</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=5u8f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u8f OCA], [http://pdbe.org/5u8f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u8f RCSB], [http://www.ebi.ac.uk/pdbsum/5u8f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u8f ProSAT]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EED ([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://proteopedia.org/fgij/fg.htm?mol=5u8f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u8f OCA], [http://pdbe.org/5u8f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u8f RCSB], [http://www.ebi.ac.uk/pdbsum/5u8f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u8f ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5u8f" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5u8f" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Polycomb\|Polycomb]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Jakob, C G]]		[[Category: Jakob, C G]]
	[[Category: Zhu, H]]		[[Category: Zhu, H]]
	[[Category: Protein binding-inhibitor complex]]		[[Category: Protein binding-inhibitor complex]]
	[[Category: Wd40 prc2]]		[[Category: Wd40 prc2]]

OCA at 21:05, 15 March 2017

OCA — Wed, 15 Mar 2017 21:05:42 GMT

←Older revision		Revision as of 21:05, 15 March 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5u8f is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Polycomb protein EED in complex with inhibitor: (3R,4S)-1-[(1S)-7-fluoro-2,3-dihydro-1H-inden-1-yl]-N,N-dimethyl-4-(1-methyl-1H-indol-3-yl)pyrrolidin-3-amine==
		+	<StructureSection load='5u8f' size='340' side='right' caption='[[5u8f]], [[Resolution\|resolution]] 1.34Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5u8f]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U8F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U8F FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=82G:(3R,4S)-1-[(1S)-7-FLUORO-2,3-DIHYDRO-1H-INDEN-1-YL]-N,N-DIMETHYL-4-(1-METHYL-1H-INDOL-3-YL)PYRROLIDIN-3-AMINE'>82G</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5u8a\|5u8a]]</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=5u8f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u8f OCA], [http://pdbe.org/5u8f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u8f RCSB], [http://www.ebi.ac.uk/pdbsum/5u8f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u8f ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://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 ==
		+	Herein we disclose SAR studies of a series of dimethylamino pyrrolidines which we recently reported as novel inhibitors of the PRC2 complex through disruption of EED/H3K27me3 binding. Modification of the indole and benzyl moieties of screening hit 1 provided analogs with substantially improved binding and cellular activities. This work culminated in the identification of compound 2, our nanomolar proof-of-concept (PoC) inhibitor which provided on-target tumor growth inhibition in a mouse xenograft model. X-ray crystal structures of several inhibitors bound in the EED active-site are also discussed.

-	~~Authors~~:	+	SAR of amino pyrrolidines as potent and novel protein-protein interaction inhibitors of the PRC2 complex through EED binding.,Curtin ML, Pliushchev MA, Li HQ, Torrent M, Dietrich JD, Jakob CG, Zhu H, Zhao H, Wang Y, Ji Z, Clark RF, Sarris KA, Selvaraju S, Shaw B, Algire MA, He Y, Richardson PL, Sweis RF, Sun C, Chiang GG, Michaelides MR Bioorg Med Chem Lett. 2017 Apr 1;27(7):1576-1583. doi:, 10.1016/j.bmcl.2017.02.030. Epub 2017 Feb 20. PMID:28254486<ref>PMID:28254486</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5u8f" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Jakob, C G]]
		+	[[Category: Zhu, H]]
		+	[[Category: Protein binding-inhibitor complex]]
		+	[[Category: Wd40 prc2]]

OCA at 14:15, 9 March 2017

OCA — Thu, 09 Mar 2017 14:15:43 GMT

←Older revision		Revision as of 14:15, 9 March 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5u8f is ON HOLD	+	The entry 5u8f is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "5u8f" [edit=sysop:move=sysop]

OCA — Thu, 22 Dec 2016 20:32:24 GMT

Protected "5u8f" [edit=sysop:move=sysop]

←Older revision

Revision as of 20:32, 22 December 2016

OCA: New page: '''Unreleased structure''' The entry 5u8f is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Thu, 22 Dec 2016 20:32:23 GMT

New page: '''Unreleased structure''' The entry 5u8f is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5u8f is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]