6pge - Revision history

OCA at 07:28, 11 October 2023

OCA — Wed, 11 Oct 2023 07:28:59 GMT

←Older revision		Revision as of 07:28, 11 October 2023
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	<StructureSection load='6pge' size='340' side='right'caption='[[6pge]], [[Resolution\|resolution]] 1.76Å' scene=''>		<StructureSection load='6pge' size='340' side='right'caption='[[6pge]], [[Resolution\|resolution]] 1.76Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6pge]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PGE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6PGE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6pge]] 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=6PGE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PGE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=OJM:ethyl+3-[4-(hydroxymethyl)-1H-imidazol-2-yl]propanoate'>OJM</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]] 1.76Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6pg3\|6pg3]]~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=OJM:ethyl+3-[4-(hydroxymethyl)-1H-imidazol-2-yl]propanoate'>OJM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6pge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pge OCA], [~~http~~://pdbe.org/6pge PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6pge RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6pge PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6pge 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=6pge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pge OCA], [https://pdbe.org/6pge PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pge RCSB], [https://www.ebi.ac.uk/pdbsum/6pge PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pge 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 6pge" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6pge" 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: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Dennis~~, M L~~]]	+	[[Category: Dennis ML]]
-	[[Category: Peat~~, T S]]~~	+	[[Category: Peat TS]]
-	~~[[Category: B-propellor]]~~	+
-	~~[[Category: Chromatin regulator]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Protein binding-inhibitor complex]]~~	+
-	~~[[Category: Scaffolding protein~~]]	+

OCA at 15:12, 11 December 2019

OCA — Wed, 11 Dec 2019 15:12:04 GMT

←Older revision		Revision as of 15:12, 11 December 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6pge is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==WDR5delta32 bound to ethyl 3-(4-(hydroxymethyl)-1H-imidazol-2-yl)propanoate==
		+	<StructureSection load='6pge' size='340' side='right'caption='[[6pge]], [[Resolution\|resolution]] 1.76Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6pge]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PGE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PGE FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=OJM:ethyl+3-[4-(hydroxymethyl)-1H-imidazol-2-yl]propanoate'>OJM</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">[[6pg3\|6pg3]]</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=6pge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pge OCA], [http://pdbe.org/6pge PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pge RCSB], [http://www.ebi.ac.uk/pdbsum/6pge PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pge 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 WD40-repeat protein WDR5 scaffolds various epigenetic writers and is a critical component of the mammalian SET/MLL histone methyltransferase complex. Dysregulation of the MLL1 catalytic function is associated with mixed-lineage leukemia, and antagonism of the WDR5-MLL1 interaction by small molecules has been proposed as a therapeutic strategy for MLL-rearranged cancers. Small molecule binders of the "WIN" site of WDR5 that cause displacement from chromatin have been additionally implicated to be of broader use in cancer treatment. In this study, a fragment screen with Surface Plasmon Resonance (SPR) was used to identify a highly ligand-efficient imidazole-containing compound that is bound in the WIN site. The subsequent medicinal chemistry campaign-guided by a suite of high-resolution cocrystal structures with WDR5-progressed the initial hit to a low micromolar binder. One outcome from this study is a moiety that substitutes well for the side chain of arginine; a tripeptide containing one such substitution was resolved in a high resolution structure (1.5 A) with a binding mode analogous to the native tripeptide. SPR furthermore indicates a similar residence time (k d = approximately 0.06 s(-1)) for these two analogs. This novel scaffold therefore represents a possible means to overcome the potential permeability issues of WDR5 ligands that possess highly basic groups like guanidine. The series reported here furthers the understanding of the WDR5 WIN site and functions as a starting point for the development of more potent WDR5 inhibitors that may serve as cancer therapeutics.

-	~~Authors~~:	+	Fragment screening for a protein-protein interaction inhibitor to WDR5.,Dennis ML, Morrow BJ, Dolezal O, Cuzzupe AN, Stupple AE, Newman J, Bentley J, Hattarki M, Nuttall SD, Foitzik RC, Street IP, Stupple PA, Monahan BJ, Peat TS Struct Dyn. 2019 Nov 14;6(6):064701. doi: 10.1063/1.5122849. eCollection 2019, Nov. PMID:31768400<ref>PMID:31768400</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6pge" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Dennis, M L]]
		+	[[Category: Peat, T S]]
		+	[[Category: B-propellor]]
		+	[[Category: Chromatin regulator]]
		+	[[Category: Inhibitor]]
		+	[[Category: Protein binding-inhibitor complex]]
		+	[[Category: Scaffolding protein]]

OCA at 04:07, 10 July 2019

OCA — Wed, 10 Jul 2019 04:07:05 GMT

←Older revision		Revision as of 04:07, 10 July 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 03 Jul 2019 04:18:01 GMT

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

←Older revision

Revision as of 04:18, 3 July 2019

OCA: New page: '''Unreleased structure''' The entry 6pge is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 03 Jul 2019 04:17:59 GMT

New page: '''Unreleased structure''' The entry 6pge is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6pge is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]