6u8b - Revision history

OCA at 07:45, 11 October 2023

OCA — Wed, 11 Oct 2023 07:45:57 GMT

←Older revision		Revision as of 07:45, 11 October 2023
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	<StructureSection load='6u8b' size='340' side='right'caption='[[6u8b]], [[Resolution\|resolution]] 1.26Å' scene=''>		<StructureSection load='6u8b' size='340' side='right'caption='[[6u8b]], [[Resolution\|resolution]] 1.26Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6u8b]] 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=6U8B OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6U8B FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6u8b]] 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=6U8B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6U8B FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=Q1M:3~~-{[~~(5-bromo-2-methoxyphenyl)sulfonyl~~]~~amino}-5-chloro-2-hydroxybenzoic+acid'>Q1M</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]] 1.261Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=Q1M:3-{[(5-bromo-2-methoxyphenyl)sulfonyl]amino}-5-chloro-2-hydroxybenzoic+acid'>Q1M</scene></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=6u8b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u8b OCA], [~~http~~://pdbe.org/6u8b PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6u8b RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6u8b PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6u8b 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=6u8b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u8b OCA], [https://pdbe.org/6u8b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6u8b RCSB], [https://www.ebi.ac.uk/pdbsum/6u8b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6u8b 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 ==
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	</div>		</div>
	<div class="pdbe-citations 6u8b" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6u8b" 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: Wang, F]]	+	[[Category: Wang F]]
-	[[Category: Zhao, B]]	+	[[Category: Zhao B]]
-	~~[[Category: High-throughput screening]]~~	+
-	~~[[Category: Myc]]~~	+
-	~~[[Category: Rbbp5]]~~	+
-	~~[[Category: Structure-based design]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Wdr5~~]]	+

OCA at 13:19, 18 December 2019

OCA — Wed, 18 Dec 2019 13:19:04 GMT

←Older revision		Revision as of 13:19, 18 December 2019
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	<StructureSection load='6u8b' size='340' side='right'caption='[[6u8b]], [[Resolution\|resolution]] 1.26Å' scene=''>		<StructureSection load='6u8b' size='340' side='right'caption='[[6u8b]], [[Resolution\|resolution]] 1.26Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6u8b]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U8B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6U8B FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6u8b]] 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=6U8B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6U8B FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Q1M:3-{[(5-bromo-2-methoxyphenyl)sulfonyl]amino}-5-chloro-2-hydroxybenzoic+acid'>Q1M</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Q1M:3-{[(5-bromo-2-methoxyphenyl)sulfonyl]amino}-5-chloro-2-hydroxybenzoic+acid'>Q1M</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6u8b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u8b OCA], [http://pdbe.org/6u8b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u8b RCSB], [http://www.ebi.ac.uk/pdbsum/6u8b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u8b 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=6u8b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u8b OCA], [http://pdbe.org/6u8b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u8b RCSB], [http://www.ebi.ac.uk/pdbsum/6u8b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u8b ProSAT]</span></td></tr>
	</table>		</table>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Wang, F]]		[[Category: Wang, F]]

OCA at 08:20, 4 December 2019

OCA — Wed, 04 Dec 2019 08:20:46 GMT

←Older revision		Revision as of 08:20, 4 December 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6u8b is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Discovery and optimization of salicyclic acid-derived sulfonamide inhibitors of the WDR5:MYC protein-protein interaction==
		+	<StructureSection load='6u8b' size='340' side='right'caption='[[6u8b]], [[Resolution\|resolution]] 1.26Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6u8b]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U8B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6U8B FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Q1M:3-{[(5-bromo-2-methoxyphenyl)sulfonyl]amino}-5-chloro-2-hydroxybenzoic+acid'>Q1M</scene></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=6u8b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u8b OCA], [http://pdbe.org/6u8b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u8b RCSB], [http://www.ebi.ac.uk/pdbsum/6u8b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u8b 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The treatment of tumors driven by overexpression or amplification of MYC oncogenes remains a significant challenge in drug discovery. Here, we present a new strategy towards the inhibition of MYC via the disruption of the protein-protein-interaction between MYC and its chromatin cofactor WDR5. Blocking the association of these proteins is hypothesized to disrupt the localization of MYC to chromatin, thus disrupting the ability of MYC to sustain tumorigenesis. Utilizing a high-throughput screening campaign and subsequent structure-guided design, we identify small molecule inhibitors of this interaction with potent in vitro binding affinity, and report structurally related negative controls that can be used to study the effect of this disruption. Our work suggests that disruption of this protein-protein interaction may provide a path toward an effective approach for the treatment of multiple tumors, and anticipate that the molecules disclosed can be used as starting points for future efforts toward compounds with improved drug-like properties.

-	~~Authors: Zhao, B~~., ~~Wang~~, F.	+	Discovery and Optimization of Salicylic Acid-Derived Sulfonamide Inhibitors of the WD Repeat-Containing Protein 5 (WDR5)-MYC Protein-Protein Interaction.,Macdonald JD, Chacon Simon S, Han C, Wang F, Shaw JG, Howes JE, Sai J, Yuh J, Camper DV, Alicie BM, Alvarado J, Nikhar S, Payne WG, Aho ER, Bauer J, Zhao B, Phan J, Thomas LR, Rossanese OW, Tansey WP, Waterson AG, Stauffer SR, Fesik SW J Med Chem. 2019 Nov 14. doi: 10.1021/acs.jmedchem.9b01411. PMID:31724864<ref>PMID:31724864</ref>

-	~~Description: Discovery and optimization of salicyclic acid-derived sulfonamide inhibitors~~ of the ~~WDR5:MYC protein-protein interaction~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~Zhao, B~~]]	+	<div class="pdbe-citations 6u8b" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Wang, F]]		[[Category: Wang, F]]
		+	[[Category: Zhao, B]]
		+	[[Category: High-throughput screening]]
		+	[[Category: Myc]]
		+	[[Category: Rbbp5]]
		+	[[Category: Structure-based design]]
		+	[[Category: Transcription]]
		+	[[Category: Wdr5]]

OCA at 03:53, 10 October 2019

OCA — Thu, 10 Oct 2019 03:53:45 GMT

←Older revision		Revision as of 03:53, 10 October 2019
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6u8b is ON HOLD	+	The entry 6u8b is ON HOLD until Paper Publication

	Authors: Zhao, B., Wang, F.		Authors: Zhao, B., Wang, F.

OCA: Protected "6u8b" [edit=sysop:move=sysop]

OCA — Wed, 02 Oct 2019 08:22:43 GMT

Protected "6u8b" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:22, 2 October 2019

OCA: New page: '''Unreleased structure''' The entry 6u8b is ON HOLD Authors: Zhao, B., Wang, F. Description: Discovery and optimization of salicyclic acid-derived sulfonamide inhibitors of the WDR5:M...

OCA — Wed, 02 Oct 2019 08:22:41 GMT

New page: '''Unreleased structure''' The entry 6u8b is ON HOLD Authors: Zhao, B., Wang, F. Description: Discovery and optimization of salicyclic acid-derived sulfonamide inhibitors of the WDR5:M...

New page

'''Unreleased structure'''

The entry 6u8b is ON HOLD

Authors: Zhao, B., Wang, F.

Description: Discovery and optimization of salicyclic acid-derived sulfonamide inhibitors of the WDR5:MYC protein-protein interaction
[[Category: Unreleased Structures]]
[[Category: Zhao, B]]
[[Category: Wang, F]]