5enf - Revision history

OCA at 08:08, 12 July 2023

OCA — Wed, 12 Jul 2023 08:08:49 GMT

←Older revision		Revision as of 08:08, 12 July 2023
Line 1:		Line 1:

	==Crystal structure of the second bromodomain of Pleckstrin homology domain interacting protein (PHIP) in complex with fragment-4 N10142 (SGC - Diamond I04-1 fragment screening)==		==Crystal structure of the second bromodomain of Pleckstrin homology domain interacting protein (PHIP) in complex with fragment-4 N10142 (SGC - Diamond I04-1 fragment screening)==
-	<StructureSection load='5enf' size='340' side='right' caption='[[5enf]], [[Resolution\|resolution]] 1.37Å' scene=''>	+	<StructureSection load='5enf' size='340' side='right'caption='[[5enf]], [[Resolution\|resolution]] 1.37Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5enf]] is a 1 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=5ENF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5ENF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5enf]] 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=5ENF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ENF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5Q7:5-AZANYL-2-(2-METHYLPROPYL)-1,3-OXAZOLE-4-CARBONITRILE'>5Q7</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 1.37Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PHIP, WDR11 ([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=5Q7:5-AZANYL-2-(2-METHYLPROPYL)-1,3-OXAZOLE-4-CARBONITRILE'>5Q7</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=5enf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5enf OCA], [~~http~~://pdbe.org/5enf PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5enf RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5enf PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5enf 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=5enf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5enf OCA], [https://pdbe.org/5enf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5enf RCSB], [https://www.ebi.ac.uk/pdbsum/5enf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5enf ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PHIP_HUMAN PHIP_HUMAN]] Probable regulator of the insulin and insulin-like growth factor signaling pathways. Stimulates cell proliferation through regulation of cyclin transcription and has an anti-apoptotic activity through AKT1 phosphorylation and activation. Plays a role in the regulation of cell morphology and cytoskeletal organization.<ref>PMID:12242307</ref> <ref>PMID:21834987</ref>	+	[https://www.uniprot.org/uniprot/PHIP_HUMAN PHIP_HUMAN] Probable regulator of the insulin and insulin-like growth factor signaling pathways. Stimulates cell proliferation through regulation of cyclin transcription and has an anti-apoptotic activity through AKT1 phosphorylation and activation. Plays a role in the regulation of cell morphology and cytoskeletal organization.<ref>PMID:12242307</ref> <ref>PMID:21834987</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5enf" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5enf" 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: Amin, J]]	+	[[Category: Large Structures]]
-	[[Category: Arrowsmith~~, C H~~]]	+	[[Category: Amin J]]
-	[[Category: Bountra, C]]	+	[[Category: Arrowsmith CH]]
-	[[Category: Bradley, A]]	+	[[Category: Bountra C]]
-	[[Category: Brennan, P]]	+	[[Category: Bradley A]]
-	[[Category: Burgess-Brown, N]]	+	[[Category: Brennan P]]
-	[[Category: Collins, P]]	+	[[Category: Burgess-Brown N]]
-	[[Category: Cox, O]]	+	[[Category: Collins P]]
-	~~[[Category: Delft, F von~~]]	+	[[Category: Cox O]]
-	[[Category: Edwards, A]]	+	[[Category: Edwards A]]
-	[[Category: Krojer, T]]	+	[[Category: Krojer T]]
-	~~[[Category: Structural genomic~~]]	+	[[Category: Spencer J]]
-	[[Category: Spencer, J]]	+	[[Category: Szykowska A]]
-	[[Category: Szykowska, A]]	+	[[Category: Talon R]]
-	[[Category: Talon, R]]	+	[[Category: Von Delft F]]
-	[[Category: ~~Bromodomain]]~~	+
-	~~[[Category: Crystallographic fragment screen]]~~	+
-	~~[[Category: Phip]]~~	+
-	~~[[Category: Sgc]]~~	+
-	~~[[Category: Signaling protein]]~~	+
-	~~[[Category: Transcription~~]]	+

OCA at 06:02, 11 July 2018

OCA — Wed, 11 Jul 2018 06:02:14 GMT

←Older revision		Revision as of 06:02, 11 July 2018
Line 3:		Line 3:
	<StructureSection load='5enf' size='340' side='right' caption='[[5enf]], [[Resolution\|resolution]] 1.37Å' scene=''>		<StructureSection load='5enf' size='340' side='right' caption='[[5enf]], [[Resolution\|resolution]] 1.37Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5enf]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ENF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ENF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5enf]] is a 1 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=5ENF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ENF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5Q7:5-AZANYL-2-(2-METHYLPROPYL)-1,3-OXAZOLE-4-CARBONITRILE'>5Q7</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5Q7:5-AZANYL-2-(2-METHYLPROPYL)-1,3-OXAZOLE-4-CARBONITRILE'>5Q7</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=5enf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5enf OCA], [http://pdbe.org/5enf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5enf RCSB], [http://www.ebi.ac.uk/pdbsum/5enf PDBsum]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PHIP, WDR11 ([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=5enf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5enf OCA], [http://pdbe.org/5enf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5enf RCSB], [http://www.ebi.ac.uk/pdbsum/5enf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5enf ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/PHIP_HUMAN PHIP_HUMAN]] Probable regulator of the insulin and insulin-like growth factor signaling pathways. Stimulates cell proliferation through regulation of cyclin transcription and has an anti-apoptotic activity through AKT1 phosphorylation and activation. Plays a role in the regulation of cell morphology and cytoskeletal organization.<ref>PMID:12242307</ref> <ref>PMID:21834987</ref>		[[http://www.uniprot.org/uniprot/PHIP_HUMAN PHIP_HUMAN]] Probable regulator of the insulin and insulin-like growth factor signaling pathways. Stimulates cell proliferation through regulation of cyclin transcription and has an anti-apoptotic activity through AKT1 phosphorylation and activation. Plays a role in the regulation of cell morphology and cytoskeletal organization.<ref>PMID:12242307</ref> <ref>PMID:21834987</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Research into the chemical biology of bromodomains has been driven by the development of acetyl-lysine mimetics. The ligands are typically anchored by binding to a highly conserved asparagine residue. Atypical bromodomains, for which the asparagine is mutated, have thus far proven elusive targets, including PHIP(2) whose parent protein, PHIP, has been linked to disease progression in diabetes and cancers. The PHIP(2) binding site contains a threonine in place of asparagine, and solution screening have yielded no convincing hits. We have overcome this hurdle by combining the sensitivity of X-ray crystallography, used as the primary fragment screen, with a strategy for rapid follow-up synthesis using a chemically-poised fragment library, which allows hits to be readily modified by parallel chemistry both peripherally and in the core. Our approach yielded the first reported hit compounds of PHIP(2) with measurable IC50 values by an AlphaScreen competition assay. The follow-up libraries of four poised fragment hits improved potency into the sub-mM range while showing good ligand efficiency and detailed structural data.
		+
		+	A poised fragment library enables rapid synthetic expansion yielding the first reported inhibitors of PHIP(2), an atypical bromodomain.,Cox OB, Krojer T, Collins P, Monteiro O, Talon R, Bradley A, Fedorov O, Amin J, Marsden BD, Spencer J, von Delft F, Brennan PE Chem Sci. 2016 Mar 1;7(3):2322-2330. doi: 10.1039/c5sc03115j. Epub 2015 Dec 22. PMID:29910922<ref>PMID:29910922</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5enf" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Amin, J]]		[[Category: Amin, J]]
	[[Category: Arrowsmith, C H]]		[[Category: Arrowsmith, C H]]

OCA at 12:03, 13 May 2016

OCA — Fri, 13 May 2016 12:03:12 GMT

←Older revision		Revision as of 12:03, 13 May 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 5enf is ON HOLD until Paper Publication~~	+	==Crystal structure of the second bromodomain of Pleckstrin homology domain interacting protein (PHIP) in complex with fragment-4 N10142 (SGC - Diamond I04-1 fragment screening)==
-		+	<StructureSection load='5enf' size='340' side='right' caption='[[5enf]], [[Resolution\|resolution]] 1.37Å' scene=''>
-	Authors: Krojer, T., Talon, R., Collins, P., Bradley, A., Cox, O., Amin, J., Szykowska, A., Burgess-Brown, N., Spencer, J., Brennan, P., Bountra, C., Arrowsmith, C.H., Edwards, A., von Delft, F., Structural Genomics Consortium (SGC)	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5enf]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ENF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ENF FirstGlance]. <br>
-	~~Description:~~ Crystal structure of the second bromodomain of Pleckstrin homology domain interacting protein (PHIP) in complex with fragment-4 N10142 (SGC -Diamond I04-1 fragment screening)	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5Q7:5-AZANYL-2-(2-METHYLPROPYL)-1,3-OXAZOLE-4-CARBONITRILE'>5Q7</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<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=5enf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5enf OCA], [http://pdbe.org/5enf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5enf RCSB], [http://www.ebi.ac.uk/pdbsum/5enf PDBsum]</span></td></tr>
-	[[~~Category~~: ~~Spencer, J~~]]	+	</table>
-	[[~~Category~~: ~~Burgess~~-~~Brown~~, N]]	+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PHIP_HUMAN PHIP_HUMAN]] Probable regulator of the insulin and insulin-like growth factor signaling pathways. Stimulates cell proliferation through regulation of cyclin transcription and has an anti-apoptotic activity through AKT1 phosphorylation and activation. Plays a role in the regulation of cell morphology and cytoskeletal organization.<ref>PMID:12242307</ref> <ref>PMID:21834987</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Amin, J]]		[[Category: Amin, J]]
-	[[Category: ~~Krojer~~, T]]	+	[[Category: Arrowsmith, C H]]
	[[Category: Bountra, C]]		[[Category: Bountra, C]]
		+	[[Category: Bradley, A]]
		+	[[Category: Brennan, P]]
		+	[[Category: Burgess-Brown, N]]
	[[Category: Collins, P]]		[[Category: Collins, P]]
	[[Category: Cox, O]]		[[Category: Cox, O]]
-	[[Category: ~~Arrowsmith~~, ~~C.H~~]]	+	[[Category: Delft, F von]]
		+	[[Category: Edwards, A]]
		+	[[Category: Krojer, T]]
		+	[[Category: Structural genomic]]
		+	[[Category: Spencer, J]]
	[[Category: Szykowska, A]]		[[Category: Szykowska, A]]
-	[[Category: Von Delft, F]]
	[[Category: Talon, R]]		[[Category: Talon, R]]
-	[[Category: ~~Bradley, A~~]]	+	[[Category: Bromodomain]]
-	[[Category: ~~Structural Genomics Consortium (~~Sgc)]]	+	[[Category: Crystallographic fragment screen]]
-	[[Category: ~~Edwards, A~~]]	+	[[Category: Phip]]
-	[[Category: ~~Brennan, P~~]]	+	[[Category: Sgc]]
		+	[[Category: Signaling protein]]
		+	[[Category: Transcription]]

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

OCA — Tue, 01 Dec 2015 03:05:58 GMT

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

←Older revision

Revision as of 03:05, 1 December 2015

OCA: New page: '''Unreleased structure''' The entry 5enf is ON HOLD until Paper Publication Authors: Krojer, T., Talon, R., Collins, P., Bradley, A., Cox, O., Amin, J., Szykowska, A., Burgess-Brown, N...

OCA — Tue, 01 Dec 2015 03:05:57 GMT

New page: '''Unreleased structure''' The entry 5enf is ON HOLD until Paper Publication Authors: Krojer, T., Talon, R., Collins, P., Bradley, A., Cox, O., Amin, J., Szykowska, A., Burgess-Brown, N...

New page

'''Unreleased structure'''

The entry 5enf is ON HOLD until Paper Publication

Authors: Krojer, T., Talon, R., Collins, P., Bradley, A., Cox, O., Amin, J., Szykowska, A., Burgess-Brown, N., Spencer, J., Brennan, P., Bountra, C., Arrowsmith, C.H., Edwards, A., von Delft, F., Structural Genomics Consortium (SGC)

Description: Crystal structure of the second bromodomain of Pleckstrin homology domain interacting protein (PHIP) in complex with fragment-4 N10142 (SGC -Diamond I04-1 fragment screening)
[[Category: Unreleased Structures]]
[[Category: Spencer, J]]
[[Category: Burgess-Brown, N]]
[[Category: Amin, J]]
[[Category: Krojer, T]]
[[Category: Bountra, C]]
[[Category: Collins, P]]
[[Category: Cox, O]]
[[Category: Arrowsmith, C.H]]
[[Category: Szykowska, A]]
[[Category: Von Delft, F]]
[[Category: Talon, R]]
[[Category: Bradley, A]]
[[Category: Structural Genomics Consortium (Sgc)]]
[[Category: Edwards, A]]
[[Category: Brennan, P]]