5wfl - Revision history

OCA at 14:12, 4 October 2023

OCA — Wed, 04 Oct 2023 14:12:02 GMT

←Older revision		Revision as of 14:12, 4 October 2023
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	<StructureSection load='5wfl' size='340' side='right'caption='[[5wfl]], [[Resolution\|resolution]] 1.93Å' scene=''>		<StructureSection load='5wfl' size='340' side='right'caption='[[5wfl]], [[Resolution\|resolution]] 1.93Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wfl]] 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=5WFL OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5WFL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wfl]] 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=5WFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WFL FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<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]] 1.93Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~KEAP1, INRF2, KIAA0132, KLHL19 ([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=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5wfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wfl OCA], [~~http~~://pdbe.org/5wfl PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5wfl RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5wfl PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5wfl 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=5wfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wfl OCA], [https://pdbe.org/5wfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wfl RCSB], [https://www.ebi.ac.uk/pdbsum/5wfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wfl ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/KEAP1_HUMAN KEAP1_HUMAN]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Allen~~, K N~~]]	+	[[Category: Allen KN]]
-	[[Category: Carolan~~, J P~~]]	+	[[Category: Carolan JP]]
-	[[Category: Lynch~~, A J]]~~	+	[[Category: Lynch AJ]]
-	~~[[Category: Scaffold]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Unliganded~~]]	+

OCA at 07:08, 15 April 2020

OCA — Wed, 15 Apr 2020 07:08:32 GMT

←Older revision		Revision as of 07:08, 15 April 2020
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	==Kelch domain of human Keap1 in open unliganded conformation==		==Kelch domain of human Keap1 in open unliganded conformation==
-	<StructureSection load='5wfl' size='340' side='right' caption='[[5wfl]], [[Resolution\|resolution]] 1.93Å' scene=''>	+	<StructureSection load='5wfl' size='340' side='right'caption='[[5wfl]], [[Resolution\|resolution]] 1.93Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wfl]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WFL OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5WFL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wfl]] 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=5WFL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5WFL FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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" id="ligandDat"><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=5wfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wfl OCA], [http://pdbe.org/5wfl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wfl RCSB], [http://www.ebi.ac.uk/pdbsum/5wfl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wfl ProSAT]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KEAP1, INRF2, KIAA0132, KLHL19 ([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://proteopedia.org/fgij/fg.htm?mol=5wfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wfl OCA], [http://pdbe.org/5wfl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wfl RCSB], [http://www.ebi.ac.uk/pdbsum/5wfl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wfl ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Development of small molecule inhibitors of protein-protein interactions (PPIs) is hampered by our poor understanding of the druggability of PPI target sites. Here, we describe the combined application of alanine-scanning mutagenesis, fragment screening, and FTMap computational hot spot mapping to evaluate the energetics and druggability of the highly charged PPI interface between Kelch-like ECH-associated protein 1 (KEAP1) and nuclear factor erythroid 2 like 2 (Nrf2), an important drug target. FTMap identifies four binding energy hot spots at the active site. Only two of these are exploited by Nrf2, which alanine scanning of both proteins shows to bind primarily through E79 and E82 interacting with KEAP1 residues S363, R380, R415, R483, and S508. We identify fragment hits and obtain X-ray complex structures for three fragments via crystal soaking using a new crystal form of KEAP1. Combining these results provides a comprehensive and quantitative picture of the origins of binding energy at the interface. Our findings additionally reveal non-native interactions that might be exploited in the design of uncharged synthetic ligands to occupy the same site on KEAP1 that has evolved to bind the highly charged DEETGE binding loop of Nrf2. These include pi-stacking with KEAP1 Y525 and interactions at an FTMap-identified hot spot deep in the binding site. Finally, we discuss how the complementary information provided by alanine-scanning mutagenesis, fragment screening, and computational hot spot mapping can be integrated to more comprehensively evaluate PPI druggability.
		+
		+	Interaction Energetics and Druggability of the Protein-Protein Interaction between Kelch-like ECH-Associated Protein 1 (KEAP1) and Nuclear Factor Erythroid 2 Like 2 (Nrf2).,Zhong M, Lynch A, Muellers SN, Jehle S, Luo L, Hall DR, Iwase R, Carolan JP, Egbert M, Wakefield A, Streu K, Harvey CM, Ortet PC, Kozakov D, Vajda S, Allen KN, Whitty A Biochemistry. 2020 Feb 4;59(4):563-581. doi: 10.1021/acs.biochem.9b00943. Epub, 2020 Jan 2. PMID:31851823<ref>PMID:31851823</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5wfl" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Kelch-like protein 3D structures\|Kelch-like protein 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Allen, K N]]		[[Category: Allen, K N]]
	[[Category: Carolan, J P]]		[[Category: Carolan, J P]]

OCA at 19:37, 19 September 2018

OCA — Wed, 19 Sep 2018 19:37:03 GMT

←Older revision		Revision as of 19:37, 19 September 2018
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-	'''Unreleased structure'''

-	~~The entry~~ 5wfl is ~~ON HOLD until Oct 12 2019~~	+	==Kelch domain of human Keap1 in open unliganded conformation==
-		+	<StructureSection load='5wfl' size='340' side='right' caption='[[5wfl]], [[Resolution\|resolution]] 1.93Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5wfl]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WFL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WFL FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5wfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wfl OCA], [http://pdbe.org/5wfl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wfl RCSB], [http://www.ebi.ac.uk/pdbsum/5wfl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wfl ProSAT]</span></td></tr>
		+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Allen, K N]]
		+	[[Category: Carolan, J P]]
		+	[[Category: Lynch, A J]]
		+	[[Category: Scaffold]]
		+	[[Category: Transcription]]
		+	[[Category: Unliganded]]

OCA at 05:52, 12 September 2018

OCA — Wed, 12 Sep 2018 05:52:05 GMT

←Older revision		Revision as of 05:52, 12 September 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5wfl is ON HOLD until ~~Sep~~ 12 2019	+	The entry 5wfl is ON HOLD until Oct 12 2019

	Authors:		Authors:

OCA at 03:50, 11 July 2018

OCA — Wed, 11 Jul 2018 03:50:49 GMT

←Older revision		Revision as of 03:50, 11 July 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5wfl is ON HOLD until ~~Paper Publication~~	+	The entry 5wfl is ON HOLD until Sep 12 2019

	Authors:		Authors:

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

OCA — Wed, 27 Sep 2017 14:46:38 GMT

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

←Older revision

Revision as of 14:46, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5wfl is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 27 Sep 2017 14:46:37 GMT

New page: '''Unreleased structure''' The entry 5wfl is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5wfl is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]