6e1y - Revision history

OCA at 06:17, 11 October 2023

2023-10-11T06:17:31Z

←Older revision		Revision as of 06:17, 11 October 2023
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	<StructureSection load='6e1y' size='340' side='right'caption='[[6e1y]], [[Resolution\|resolution]] 1.22Å' scene=''>		<StructureSection load='6e1y' size='340' side='right'caption='[[6e1y]], [[Resolution\|resolution]] 1.22Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6e1y]] 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=6E1Y OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6E1Y FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6e1y]] 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=6E1Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E1Y FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=HLM:N~~-[~~(1S)-1-(3-chlorophenyl)ethyl]-3-{~~[~~(4,5-dihydro-1H-imidazol-2-yl)amino~~]~~methyl}benzamide'>HLM</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]] 1.219Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~>[[6d9x\|6d9x]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HLM:N-[(1S)-1-(3-chlorophenyl)ethyl]-3-{[(4,5-dihydro-1H-imidazol-2-yl)amino]methyl}benzamide'>HLM</scene></td></tr>
-	~~<tr~~ id~~='gene'><td class~~="~~sblockLbl~~"><b>[[~~Gene\|Gene:]~~]~~</b~~></td>~~<td class="sblockDat">WDR5, BIG3 ([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=6e1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e1y OCA], [https://pdbe.org/6e1y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e1y RCSB], [https://www.ebi.ac.uk/pdbsum/6e1y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e1y 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=6e1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e1y OCA], [~~http~~://pdbe.org/6e1y PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6e1y RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6e1y PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6e1y ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/WDR5_HUMAN WDR5_HUMAN]] Contributes to histone modification. May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4'. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. May regulate osteoblasts differentiation.<ref>PMID:19556245</ref> <ref>PMID:19103755</ref> <ref>PMID:20018852</ref> <ref>PMID:16600877</ref> <ref>PMID:16829960</ref>	+	[https://www.uniprot.org/uniprot/WDR5_HUMAN WDR5_HUMAN] Contributes to histone modification. May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4'. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. May regulate osteoblasts differentiation.<ref>PMID:19556245</ref> <ref>PMID:19103755</ref> <ref>PMID:20018852</ref> <ref>PMID:16600877</ref> <ref>PMID:16829960</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6e1y" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6e1y" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[WD-repeat protein 3D structures\|WD-repeat protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Fesik~~, S W~~]]	+	[[Category: Fesik SW]]
-	[[Category: Phan, J]]	+	[[Category: Phan J]]
-	~~[[Category: Dna binding protein]]~~	+
-	~~[[Category: Dna binding protein-inhibitor complex]]~~	+
-	~~[[Category: Fragment screening]]~~	+
-	~~[[Category: Gene regulation]]~~	+
-	~~[[Category: Gene regulation-inhibitor complex]]~~	+
-	~~[[Category: Mixed-lineage leukemia]]~~	+
-	~~[[Category: Structure-based design]]~~	+
-	~~[[Category: Wdr5]]~~	+
-	~~[[Category: Win-site~~]]	+

OCA at 08:21, 20 March 2019

2019-03-20T08:21:28Z

←Older revision		Revision as of 08:21, 20 March 2019
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	<StructureSection load='6e1y' size='340' side='right'caption='[[6e1y]], [[Resolution\|resolution]] 1.22Å' scene=''>		<StructureSection load='6e1y' size='340' side='right'caption='[[6e1y]], [[Resolution\|resolution]] 1.22Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6e1y]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E1Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E1Y FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6e1y]] 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=6E1Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E1Y FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HLM:N-[(1S)-1-(3-chlorophenyl)ethyl]-3-{[(4,5-dihydro-1H-imidazol-2-yl)amino]methyl}benzamide'>HLM</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HLM:N-[(1S)-1-(3-chlorophenyl)ethyl]-3-{[(4,5-dihydro-1H-imidazol-2-yl)amino]methyl}benzamide'>HLM</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6d9x\|6d9x]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6d9x\|6d9x]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">WDR5, BIG3 ([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=6e1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e1y OCA], [http://pdbe.org/6e1y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e1y RCSB], [http://www.ebi.ac.uk/pdbsum/6e1y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e1y 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=6e1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e1y OCA], [http://pdbe.org/6e1y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e1y RCSB], [http://www.ebi.ac.uk/pdbsum/6e1y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e1y ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/WDR5_HUMAN WDR5_HUMAN]] Contributes to histone modification. May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4'. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. May regulate osteoblasts differentiation.<ref>PMID:19556245</ref> <ref>PMID:19103755</ref> <ref>PMID:20018852</ref> <ref>PMID:16600877</ref> <ref>PMID:16829960</ref>		[[http://www.uniprot.org/uniprot/WDR5_HUMAN WDR5_HUMAN]] Contributes to histone modification. May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4'. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. May regulate osteoblasts differentiation.<ref>PMID:19556245</ref> <ref>PMID:19103755</ref> <ref>PMID:20018852</ref> <ref>PMID:16600877</ref> <ref>PMID:16829960</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The chromatin-associated protein WDR5 is a promising target for pharmacological inhibition in cancer. Drug discovery efforts center on the blockade of the "WIN site" of WDR5, a well-defined pocket that is amenable to small molecule inhibition. Various cancer contexts have been proposed to be targets for WIN site inhibitors, but a lack of understanding of WDR5 target genes and of the primary effects of WIN site inhibitors hampers their utility. Here, by the discovery of potent WIN site inhibitors, we demonstrate that the WIN site links WDR5 to chromatin at a small cohort of loci, including a specific subset of ribosome protein genes. WIN site inhibitors rapidly displace WDR5 from chromatin and decrease the expression of associated genes, causing translational inhibition, nucleolar stress, and p53 induction. Our studies define a mode by which WDR5 engages chromatin and forecast that WIN site blockade could have utility against multiple cancer types.
		+
		+	Displacement of WDR5 from Chromatin by a WIN Site Inhibitor with Picomolar Affinity.,Aho ER, Wang J, Gogliotti RD, Howard GC, Phan J, Acharya P, Macdonald JD, Cheng K, Lorey SL, Lu B, Wenzel S, Foshage AM, Alvarado J, Wang F, Shaw JG, Zhao B, Weissmiller AM, Thomas LR, Vakoc CR, Hall MD, Hiebert SW, Liu Q, Stauffer SR, Fesik SW, Tansey WP Cell Rep. 2019 Mar 12;26(11):2916-2928.e13. doi: 10.1016/j.celrep.2019.02.047. PMID:30865883<ref>PMID:30865883</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6e1y" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Fesik, S W]]		[[Category: Fesik, S W]]

OCA at 11:56, 13 March 2019

2019-03-13T11:56:12Z

←Older revision		Revision as of 11:56, 13 March 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 6e1y is ON HOLD until Paper Publication~~	+	==Discovery of Potent 2-Aryl-6,7-Dihydro-5HPyrrolo[ 1,2-a]imidazoles as WDR5 WIN-site Inhibitors Using Fragment-Based Methods and Structure-Based Design==
-		+	<StructureSection load='6e1y' size='340' side='right'caption='[[6e1y]], [[Resolution\|resolution]] 1.22Å' scene=''>
-	~~Authors: Phan, J., Fesik, S.W.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6e1y]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E1Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E1Y FirstGlance]. <br>
-	~~Description:~~ Discovery of Potent 2-Aryl-6,7-Dihydro-5HPyrrolo[ 1,2-a]imidazoles as WDR5 WIN-site Inhibitors Using Fragment-Based Methods and Structure-Based Design	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HLM:N-[(1S)-1-(3-chlorophenyl)ethyl]-3-{[(4,5-dihydro-1H-imidazol-2-yl)amino]methyl}benzamide'>HLM</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6d9x\|6d9x]]</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=6e1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e1y OCA], [http://pdbe.org/6e1y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e1y RCSB], [http://www.ebi.ac.uk/pdbsum/6e1y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e1y ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/WDR5_HUMAN WDR5_HUMAN]] Contributes to histone modification. May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4'. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. May regulate osteoblasts differentiation.<ref>PMID:19556245</ref> <ref>PMID:19103755</ref> <ref>PMID:20018852</ref> <ref>PMID:16600877</ref> <ref>PMID:16829960</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Fesik, S W]]
	[[Category: Phan, J]]		[[Category: Phan, J]]
-	[[Category: ~~Fesik, S.W~~]]	+	[[Category: Dna binding protein]]
		+	[[Category: Dna binding protein-inhibitor complex]]
		+	[[Category: Fragment screening]]
		+	[[Category: Gene regulation]]
		+	[[Category: Gene regulation-inhibitor complex]]
		+	[[Category: Mixed-lineage leukemia]]
		+	[[Category: Structure-based design]]
		+	[[Category: Wdr5]]
		+	[[Category: Win-site]]

OCA at 05:52, 25 July 2018

2018-07-25T05:52:15Z

←Older revision		Revision as of 05:52, 25 July 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6e1y is ON HOLD	+	The entry 6e1y is ON HOLD until Paper Publication

	Authors: Phan, J., Fesik, S.W.		Authors: Phan, J., Fesik, S.W.
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	Description: Discovery of Potent 2-Aryl-6,7-Dihydro-5HPyrrolo[ 1,2-a]imidazoles as WDR5 WIN-site Inhibitors Using Fragment-Based Methods and Structure-Based Design		Description: Discovery of Potent 2-Aryl-6,7-Dihydro-5HPyrrolo[ 1,2-a]imidazoles as WDR5 WIN-site Inhibitors Using Fragment-Based Methods and Structure-Based Design
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Fesik, S.W]]
	[[Category: Phan, J]]		[[Category: Phan, J]]
		+	[[Category: Fesik, S.W]]

OCA: Protected "6e1y" [edit=sysop:move=sysop]

2018-07-18T05:40:41Z

Protected "6e1y" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:40, 18 July 2018

OCA: New page: '''Unreleased structure''' The entry 6e1y is ON HOLD Authors: Phan, J., Fesik, S.W. Description: Discovery of Potent 2-Aryl-6,7-Dihydro-5HPyrrolo[ 1,2-a]imidazoles as WDR5 WIN-site Inh...

2018-07-18T05:40:40Z

New page: '''Unreleased structure''' The entry 6e1y is ON HOLD Authors: Phan, J., Fesik, S.W. Description: Discovery of Potent 2-Aryl-6,7-Dihydro-5HPyrrolo[ 1,2-a]imidazoles as WDR5 WIN-site Inh...

New page

'''Unreleased structure'''

The entry 6e1y is ON HOLD

Authors: Phan, J., Fesik, S.W.

Description: Discovery of Potent 2-Aryl-6,7-Dihydro-5HPyrrolo[ 1,2-a]imidazoles as WDR5 WIN-site Inhibitors Using Fragment-Based Methods and Structure-Based Design
[[Category: Unreleased Structures]]
[[Category: Fesik, S.W]]
[[Category: Phan, J]]