OCA at 15:16, 18 October 2023

OCA — Wed, 18 Oct 2023 15:16:14 GMT

←Older revision		Revision as of 15:16, 18 October 2023
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-	====	+	==Kelch domain of human KEAP1 bound to Nrf2 peptide, LDEETGEAL==
-	<StructureSection load='7k29' size='340' side='right'caption='[[7k29]]' scene=''>	+	<StructureSection load='7k29' size='340' side='right'caption='[[7k29]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7k29]] is a 3 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=7K29 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K29 FirstGlance]. <br>
-	</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=7k29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k29 OCA], [https://pdbe.org/7k29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k29 RCSB], [https://www.ebi.ac.uk/pdbsum/7k29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k29 ProSAT]</span></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]] 2.2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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'>[https://proteopedia.org/fgij/fg.htm?mol=7k29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k29 OCA], [https://pdbe.org/7k29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k29 RCSB], [https://www.ebi.ac.uk/pdbsum/7k29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k29 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/KEAP1_HUMAN KEAP1_HUMAN]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Macrocycles, including macrocyclic peptides, have shown promise for targeting challenging protein-protein interactions (PPIs). One PPI of high interest is between Kelch-like ECH-Associated Protein-1 (KEAP1) and Nuclear Factor (Erythroid-derived 2)-like 2 (Nrf2). Guided by X-ray crystallography, NMR, modeling, and machine learning, we show that the full 20 nM binding affinity of Nrf2 for KEAP1 can be recapitulated in a cyclic 7-mer peptide, c[(D)-beta-homoAla-DPETGE]. This compound was identified from the Nrf2-derived linear peptide GDEETGE (K(D) = 4.3 muM) solely by optimizing the conformation of the cyclic compound, without changing any KEAP1 interacting residue. X-ray crystal structures were determined for each linear and cyclic peptide variant bound to KEAP1. Despite large variations in affinity, no obvious differences in the conformation of the peptide binding residues or in the interactions they made with KEAP1 were observed. However, analysis of the X-ray structures by machine learning showed that locations of strain in the bound ligand could be identified through patterns of subangstrom distortions from the geometry observed for unstrained linear peptides. We show that optimizing the cyclic peptide affinity was driven partly through conformational preorganization associated with a proline substitution at position 78 and with the geometry of the noninteracting residue Asp77 and partly by decreasing strain in the ETGE motif itself. This approach may have utility in dissecting the trade-off between conformational preorganization and strain in other ligand-receptor systems. We also identify a pair of conserved hydrophobic residues flanking the core DxETGE motif which play a conformational role in facilitating the high-affinity binding of Nrf2 to KEAP1.
		+
		+	Recapitulating the Binding Affinity of Nrf2 for KEAP1 in a Cyclic Heptapeptide, Guided by NMR, X-ray Crystallography, and Machine Learning.,Ortet PC, Muellers SN, Viarengo-Baker LA, Streu K, Szymczyna BR, Beeler AB, Allen KN, Whitty A J Am Chem Soc. 2021 Mar 17;143(10):3779-3793. doi: 10.1021/jacs.0c09799. Epub , 2021 Mar 8. PMID:33683866<ref>PMID:33683866</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7k29" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Kelch-like protein 3D structures\|Kelch-like protein 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Allen KN]]
		+	[[Category: Muellers SN]]

OCA at 06:52, 7 April 2021

OCA — Wed, 07 Apr 2021 06:52:02 GMT

←Older revision		Revision as of 06:52, 7 April 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7k29 ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7k29' size='340' side='right'caption='[[7k29]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~:	+	</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=7k29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k29 OCA], [https://pdbe.org/7k29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k29 RCSB], [https://www.ebi.ac.uk/pdbsum/7k29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k29 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 04:43, 7 October 2020

OCA — Wed, 07 Oct 2020 04:43:09 GMT

←Older revision		Revision as of 04:43, 7 October 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7k29 is ON HOLD	+	The entry 7k29 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7k29" [edit=sysop:move=sysop]

OCA — Wed, 16 Sep 2020 07:07:51 GMT

Protected "7k29" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:07, 16 September 2020

OCA: New page: '''Unreleased structure''' The entry 7k29 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 16 Sep 2020 07:07:50 GMT

New page: '''Unreleased structure''' The entry 7k29 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7k29 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7k29 - Revision history

OCA at 15:16, 18 October 2023

OCA at 06:52, 7 April 2021

OCA at 04:43, 7 October 2020

OCA: Protected "7k29" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7k29 is ON HOLD Authors: Description: Category: Unreleased Structures