6e22 - Revision history

OCA at 06:17, 11 October 2023

2023-10-11T06:17:34Z

←Older revision		Revision as of 06:17, 11 October 2023
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	<StructureSection load='6e22' size='340' side='right'caption='[[6e22]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='6e22' size='340' side='right'caption='[[6e22]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6e22]] 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=6E22 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6E22 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6e22]] 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=6E22 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E22 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HLS:3-{[(4,5-dihydro-1H-imidazol-2-yl)amino]methyl}-N-[(3,5-dimethoxyphenyl)methyl]-4-fluorobenzamide'>HLS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.6Å</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=HLS:3-{[(4,5-dihydro-1H-imidazol-2-yl)amino]methyl}-N-[(3,5-dimethoxyphenyl)methyl]-4-fluorobenzamide'>HLS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6e22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e22 OCA], [https://pdbe.org/6e22 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e22 RCSB], [https://www.ebi.ac.uk/pdbsum/6e22 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e22 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=6e22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e22 OCA], [~~http~~://pdbe.org/6e22 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6e22 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6e22 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6e22 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 6e22" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6e22" 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

2019-03-20T08:21:32Z

←Older revision		Revision as of 08:21, 20 March 2019
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	<StructureSection load='6e22' size='340' side='right'caption='[[6e22]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='6e22' size='340' side='right'caption='[[6e22]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6e22]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E22 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E22 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6e22]] 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=6E22 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E22 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HLS:3-{[(4,5-dihydro-1H-imidazol-2-yl)amino]methyl}-N-[(3,5-dimethoxyphenyl)methyl]-4-fluorobenzamide'>HLS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HLS:3-{[(4,5-dihydro-1H-imidazol-2-yl)amino]methyl}-N-[(3,5-dimethoxyphenyl)methyl]-4-fluorobenzamide'>HLS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6e22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e22 OCA], [http://pdbe.org/6e22 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e22 RCSB], [http://www.ebi.ac.uk/pdbsum/6e22 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e22 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=6e22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e22 OCA], [http://pdbe.org/6e22 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e22 RCSB], [http://www.ebi.ac.uk/pdbsum/6e22 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e22 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 6e22" 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

2019-03-13T11:56:23Z

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

-	~~The entry~~ 6e22 is ~~ON HOLD until Paper Publication~~	+	==Displacement of WDR5 from chromatin by a pharmacological WIN site inhibitor with picomolar affinity==
-		+	<StructureSection load='6e22' size='340' side='right'caption='[[6e22]], [[Resolution\|resolution]] 1.60Å' scene=''>
-	~~Authors~~: ~~Phan~~, J., ~~Fesik~~, S.W.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6e22]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E22 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E22 FirstGlance]. <br>
-	~~Description~~: ~~Displacement~~ of ~~WDR5 from chromatin by~~ a ~~pharmacological WIN site inhibitor with picomolar affinity~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HLS:3-{[(4,5-dihydro-1H-imidazol-2-yl)amino]methyl}-N-[(3,5-dimethoxyphenyl)methyl]-4-fluorobenzamide'>HLS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6e22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e22 OCA], [http://pdbe.org/6e22 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e22 RCSB], [http://www.ebi.ac.uk/pdbsum/6e22 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e22 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

2018-07-25T05:52:21Z

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

-	The entry 6e22 is ON HOLD	+	The entry 6e22 is ON HOLD until Paper Publication

	Authors: Phan, J., Fesik, S.W.		Authors: Phan, J., Fesik, S.W.
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	Description: Displacement of WDR5 from chromatin by a pharmacological WIN site inhibitor with picomolar affinity		Description: Displacement of WDR5 from chromatin by a pharmacological WIN site inhibitor with picomolar affinity
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Fesik, S.W]]
	[[Category: Phan, J]]		[[Category: Phan, J]]
		+	[[Category: Fesik, S.W]]

OCA: Protected "6e22" [edit=sysop:move=sysop]

2018-07-18T05:40:59Z

Protected "6e22" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:40, 18 July 2018

OCA: New page: '''Unreleased structure''' The entry 6e22 is ON HOLD Authors: Phan, J., Fesik, S.W. Description: Displacement of WDR5 from chromatin by a pharmacological WIN site inhibitor with picomo...

2018-07-18T05:40:58Z

New page: '''Unreleased structure''' The entry 6e22 is ON HOLD Authors: Phan, J., Fesik, S.W. Description: Displacement of WDR5 from chromatin by a pharmacological WIN site inhibitor with picomo...

New page

'''Unreleased structure'''

The entry 6e22 is ON HOLD

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

Description: Displacement of WDR5 from chromatin by a pharmacological WIN site inhibitor with picomolar affinity
[[Category: Unreleased Structures]]
[[Category: Fesik, S.W]]
[[Category: Phan, J]]