5wuk - Revision history

OCA at 07:17, 7 October 2020

OCA — Wed, 07 Oct 2020 07:17:36 GMT

←Older revision		Revision as of 07:17, 7 October 2020
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	==Crystal structure of EED [G255D] in complex with EZH2 peptide and EED226 compound==		==Crystal structure of EED [G255D] in complex with EZH2 peptide and EED226 compound==
-	<StructureSection load='5wuk' size='340' side='right' caption='[[5wuk]], [[Resolution\|resolution]] 2.03Å' scene=''>	+	<StructureSection load='5wuk' size='340' side='right'caption='[[5wuk]], [[Resolution\|resolution]] 2.03Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wuk]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WUK OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5WUK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wuk]] 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=5WUK OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5WUK FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=73K:N-(FURAN-2-YLMETHYL)-8-(4-METHYLSULFONYLPHENYL)-[1,2,4]TRIAZOLO[4,3-C]PYRIMIDIN-5-AMINE'>73K</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=73K:N-(FURAN-2-YLMETHYL)-8-(4-METHYLSULFONYLPHENYL)-[1,2,4]TRIAZOLO[4,3-C]PYRIMIDIN-5-AMINE'>73K</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </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=5wuk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wuk OCA], [http://pdbe.org/5wuk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wuk RCSB], [http://www.ebi.ac.uk/pdbsum/5wuk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wuk 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=5wuk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wuk OCA], [http://pdbe.org/5wuk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wuk RCSB], [http://www.ebi.ac.uk/pdbsum/5wuk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wuk ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	</div>		</div>
	<div class="pdbe-citations 5wuk" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5wuk" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Polycomb\|Polycomb]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Histone-lysine N-methyltransferase]]		[[Category: Histone-lysine N-methyltransferase]]
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Chen, Z]]		[[Category: Chen, Z]]
	[[Category: Eed]]		[[Category: Eed]]
	[[Category: Gene regulation]]		[[Category: Gene regulation]]

OCA at 13:03, 4 May 2017

OCA — Thu, 04 May 2017 13:03:34 GMT

←Older revision		Revision as of 13:03, 4 May 2017
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-	'''Unreleased structure'''

-	The entry ~~5wuk~~ is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of EED [G255D] in complex with EZH2 peptide and EED226 compound==
		+	<StructureSection load='5wuk' size='340' side='right' caption='[[5wuk]], [[Resolution\|resolution]] 2.03Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5wuk]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WUK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WUK FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=73K:N-(FURAN-2-YLMETHYL)-8-(4-METHYLSULFONYLPHENYL)-[1,2,4]TRIAZOLO[4,3-C]PYRIMIDIN-5-AMINE'>73K</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </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=5wuk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wuk OCA], [http://pdbe.org/5wuk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wuk RCSB], [http://www.ebi.ac.uk/pdbsum/5wuk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wuk ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/EZH2_HUMAN EZH2_HUMAN]] Weaver syndrome. The disease is caused by mutations affecting the gene represented in this entry.
		+	== 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> [[http://www.uniprot.org/uniprot/EZH2_HUMAN EZH2_HUMAN]] Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Compared to EZH2-containing complexes, it is more abundant in embryonic stem cells and plays a major role in forming H3K27me3, which is required for embryonic stem cell identity and proper differentiation. 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, CDKN2A and retinoic acid target genes. EZH2 can also methylate non-histone proteins such as the transcription factor GATA4 and the nuclear receptor RORA.<ref>PMID:14532106</ref> <ref>PMID:15385962</ref> <ref>PMID:15231737</ref> <ref>PMID:15225548</ref> <ref>PMID:16179254</ref> <ref>PMID:16618801</ref> <ref>PMID:16357870</ref> <ref>PMID:16936726</ref> <ref>PMID:17210787</ref> <ref>PMID:17344414</ref> <ref>PMID:19026781</ref> <ref>PMID:18285464</ref> <ref>PMID:20935635</ref> <ref>PMID:23063525</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The EED (embryonic ectoderm development) subunit of the Polycomb repressive complex 2 (PRC2) plays an important role in the feed forward regulation of the PRC2 enzymatic activity. We recently identified a new class of allosteric PRC2 inhibitors that bind to the H3K27me3 pocket of EED. Multiple assays were developed and used to identify and characterize this type of PRC2 inhibitors. One of them is a genetically encoded EED biosensor based on the EED[G255D] mutant and the split firefly luciferase. This EED biosensor can detect the compound binding in the transfected cells and in the in vitro biochemical assays. Compared to other commonly used cellular assays, the EED biosensor assay has the advantage of shorter compound incubation with cells. The in vitro EED biosensor is much more sensitive than other label-free biophysical assays (e.g. DSF, ITC). Based on the crystal structure, the DSF data as well as the biosensor assay data, it's most likely that compound-induced increase in the luciferase activity of the EED[G255D] biosensor results from the decreased non-productive interactions between the EED subdomain and other subdomains within the biosensor construct. This new insight of the mechanism might help to broaden the use of the split luciferase based biosensors.

-	~~Authors~~:	+	Split luciferase-based biosensors for characterizing EED binders.,Li L, Feng L, Shi M, Zeng J, Chen Z, Zhong L, Huang L, Guo W, Huang Y, Qi W, Lu C, Li E, Zhao K, Gu J Anal Biochem. 2017 Apr 1;522:37-45. doi: 10.1016/j.ab.2017.01.014. Epub 2017 Jan , 19. PMID:28111304<ref>PMID:28111304</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5wuk" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Histone-lysine N-methyltransferase]]
		+	[[Category: Chen, Z]]
		+	[[Category: Eed]]
		+	[[Category: Gene regulation]]

OCA at 15:22, 9 March 2017

OCA — Thu, 09 Mar 2017 15:22:07 GMT

←Older revision		Revision as of 15:22, 9 March 2017
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Mon, 02 Jan 2017 15:29:48 GMT

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

←Older revision

Revision as of 15:29, 2 January 2017

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

OCA — Mon, 02 Jan 2017 15:29:47 GMT

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

New page

'''Unreleased structure'''

The entry 5wuk is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]