5cgj - Revision history

OCA at 11:45, 9 May 2024

OCA — Thu, 09 May 2024 11:45:00 GMT

←Older revision		Revision as of 11:45, 9 May 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5cgj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CGJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CGJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[5cgj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CGJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CGJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=51M:(3S)-1-(4-{[(2,3,5,6-TETRAMETHYLPHENYL)SULFONYL]AMINO}NAPHTHALEN-1-YL)PYRROLIDINE-3-CARBOXYLIC+ACID'>51M</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]] 3.36Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=51M:(3S)-1-(4-{[(2,3,5,6-TETRAMETHYLPHENYL)SULFONYL]AMINO}NAPHTHALEN-1-YL)PYRROLIDINE-3-CARBOXYLIC+ACID'>51M</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=5cgj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cgj OCA], [https://pdbe.org/5cgj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cgj RCSB], [https://www.ebi.ac.uk/pdbsum/5cgj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cgj 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=5cgj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cgj OCA], [https://pdbe.org/5cgj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cgj RCSB], [https://www.ebi.ac.uk/pdbsum/5cgj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cgj ProSAT]</span></td></tr>
	</table>		</table>

OCA at 12:05, 14 June 2023

OCA — Wed, 14 Jun 2023 12:05:18 GMT

←Older revision		Revision as of 12:05, 14 June 2023
Line 3:		Line 3:
	<StructureSection load='5cgj' size='340' side='right'caption='[[5cgj]], [[Resolution\|resolution]] 3.36Å' scene=''>		<StructureSection load='5cgj' size='340' side='right'caption='[[5cgj]], [[Resolution\|resolution]] 3.36Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5cgj]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Lk3_transgenic_mice Lk3 transgenic mice~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CGJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5CGJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5cgj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CGJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CGJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=51M:(3S)-1-(4-{[(2,3,5,6-TETRAMETHYLPHENYL)SULFONYL]AMINO}NAPHTHALEN-1-YL)PYRROLIDINE-3-CARBOXYLIC+ACID'>51M</scene>, <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=51M:(3S)-1-(4-{[(2,3,5,6-TETRAMETHYLPHENYL)SULFONYL]AMINO}NAPHTHALEN-1-YL)PYRROLIDINE-3-CARBOXYLIC+ACID'>51M</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Keap1, Inrf2, Kiaa0132 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=5cgj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cgj OCA], [https://pdbe.org/5cgj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cgj RCSB], [https://www.ebi.ac.uk/pdbsum/5cgj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cgj 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=5cgj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cgj OCA], [~~http~~://pdbe.org/5cgj PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5cgj RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5cgj PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5cgj ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/KEAP1_MOUSE KEAP1_MOUSE]] Retains NFE2L2/NRF2 in the cytosol. Functions as substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1. Targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. May also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome (By similarity).<ref>PMID:9887101</ref> <ref>PMID:12682069</ref>	+	[https://www.uniprot.org/uniprot/KEAP1_MOUSE KEAP1_MOUSE] Retains NFE2L2/NRF2 in the cytosol. Functions as substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1. Targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. May also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome (By similarity).<ref>PMID:9887101</ref> <ref>PMID:12682069</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 26:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Lk3 transgenic mice~~]]	+	[[Category: Mus musculus]]
-	[[Category: Engel~~, C K~~]]	+	[[Category: Engel CK]]
-	[[Category: Loenze, P]]	+	[[Category: Loenze P]]
-	[[Category: Schimanski-Breves, S]]	+	[[Category: Schimanski-Breves S]]
-	~~[[Category: Beta propeller]]~~	+
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Protein binding~~]]	+

OCA at 11:37, 27 March 2020

OCA — Fri, 27 Mar 2020 11:37:22 GMT

←Older revision		Revision as of 11:37, 27 March 2020
Line 1:		Line 1:
		+
	==Crystal structure of murine Keap1 in complex with RA839, a non-covalent small-molecule binder to Keap1 and selective activator of Nrf2 signalling.==		==Crystal structure of murine Keap1 in complex with RA839, a non-covalent small-molecule binder to Keap1 and selective activator of Nrf2 signalling.==
-	<StructureSection load='5cgj' size='340' side='right' caption='[[5cgj]], [[Resolution\|resolution]] 3.36Å' scene=''>	+	<StructureSection load='5cgj' size='340' side='right'caption='[[5cgj]], [[Resolution\|resolution]] 3.36Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5cgj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CGJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CGJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5cgj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CGJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CGJ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=51M:(3S)-1-(4-{[(2,3,5,6-TETRAMETHYLPHENYL)SULFONYL]AMINO}NAPHTHALEN-1-YL)PYRROLIDINE-3-CARBOXYLIC+ACID'>51M</scene>, <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"><scene name='pdbligand=51M:(3S)-1-(4-{[(2,3,5,6-TETRAMETHYLPHENYL)SULFONYL]AMINO}NAPHTHALEN-1-YL)PYRROLIDINE-3-CARBOXYLIC+ACID'>51M</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=5cgj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cgj OCA], [http://pdbe.org/5cgj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cgj RCSB], [http://www.ebi.ac.uk/pdbsum/5cgj PDBsum]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Keap1, Inrf2, Kiaa0132 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=5cgj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cgj OCA], [http://pdbe.org/5cgj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cgj RCSB], [http://www.ebi.ac.uk/pdbsum/5cgj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cgj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5cgj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5cgj" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Kelch-like protein 3D structures\|Kelch-like protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Lk3 transgenic mice]]
	[[Category: Engel, C K]]		[[Category: Engel, C K]]
	[[Category: Loenze, P]]		[[Category: Loenze, P]]

OCA at 21:08, 30 November 2015

OCA — Mon, 30 Nov 2015 21:08:00 GMT

←Older revision		Revision as of 21:08, 30 November 2015
Line 8:		Line 8:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/KEAP1_MOUSE KEAP1_MOUSE]] Retains NFE2L2/NRF2 in the cytosol. Functions as substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1. Targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. May also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome (By similarity).<ref>PMID:9887101</ref> <ref>PMID:12682069</ref>		[[http://www.uniprot.org/uniprot/KEAP1_MOUSE KEAP1_MOUSE]] Retains NFE2L2/NRF2 in the cytosol. Functions as substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1. Targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. May also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome (By similarity).<ref>PMID:9887101</ref> <ref>PMID:12682069</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The activation of the transcription factor NF-E2-related factor 2 (Nrf2) maintains cellular homeostasis in response to oxidative stress by the regulation of multiple cytoprotective genes. Without stressors, the activity of Nrf2 is inhibited by its interaction with the Keap1 (kelch-like ECH-associated protein 1). Here, we describe (3S)-1-[4-[(2,3,5,6-tetramethylphenyl) sulfonylamino]-1-naphthyl]pyrrolidine-3-carboxylic acid (RA839), a small molecule that binds noncovalently to the Nrf2-interacting kelch domain of Keap1 with a Kd of approximately 6 mum, as demonstrated by x-ray co-crystallization and isothermal titration calorimetry. Whole genome DNA arrays showed that at 10 mum RA839 significantly regulated 105 probe sets in bone marrow-derived macrophages. Canonical pathway mapping of these probe sets revealed an activation of pathways linked with Nrf2 signaling. These pathways were also activated after the activation of Nrf2 by the silencing of Keap1 expression. RA839 regulated only two genes in Nrf2 knock-out macrophages. Similar to the activation of Nrf2 by either silencing of Keap1 expression or by the reactive compound 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid methyl ester (CDDO-Me), RA839 prevented the induction of both inducible nitric-oxide synthase expression and nitric oxide release in response to lipopolysaccharides in macrophages. In mice, RA839 acutely induced Nrf2 target gene expression in liver. RA839 is a selective inhibitor of the Keap1/Nrf2 interaction and a useful tool compound to study the biology of Nrf2.
		+
		+	Characterization of RA839, a Noncovalent Small Molecule Binder to Keap1 and Selective Activator of Nrf2 Signaling.,Winkel AF, Engel CK, Margerie D, Kannt A, Szillat H, Glombik H, Kallus C, Ruf S, Gussregen S, Riedel J, Herling AW, von Knethen A, Weigert A, Brune B, Schmoll D J Biol Chem. 2015 Nov 20;290(47):28446-55. doi: 10.1074/jbc.M115.678136. Epub, 2015 Oct 12. PMID:26459563<ref>PMID:26459563</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5cgj" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 05:33, 22 October 2015

OCA — Thu, 22 Oct 2015 05:33:29 GMT

←Older revision		Revision as of 05:33, 22 October 2015
Line 1:		Line 1:
-	'''~~Unreleased structure~~'''	+	==Crystal structure of murine Keap1 in complex with RA839, a non-covalent small-molecule binder to Keap1 and selective activator of Nrf2 signalling.==
-		+	<StructureSection load='5cgj' size='340' side='right' caption='[[5cgj]], [[Resolution\|resolution]] 3.36Å' scene=''>
-	~~The entry~~ 5cgj is ~~ON HOLD until Jul 09 2017~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5cgj]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CGJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CGJ FirstGlance]. <br>
-	~~Authors~~: ~~Schimanski~~-~~Breves~~, S., ~~Loenze, P~~., ~~Engel~~, C.K.	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=51M:(3S)-1-(4-{[(2,3,5,6-TETRAMETHYLPHENYL)SULFONYL]AMINO}NAPHTHALEN-1-YL)PYRROLIDINE-3-CARBOXYLIC+ACID'>51M</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=5cgj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cgj OCA], [http://pdbe.org/5cgj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cgj RCSB], [http://www.ebi.ac.uk/pdbsum/5cgj PDBsum]</span></td></tr>
-	~~Description~~: ~~Crystal structure of murine Keap1~~ in complex ~~with RA839~~, ~~a non-covalent small-molecule binder to Keap1~~ and ~~selective activator~~ of ~~Nrf2 signalling~~.	+	</table>
-	[[Category: ~~Unreleased Structures~~]]	+	== Function ==
		+	[[http://www.uniprot.org/uniprot/KEAP1_MOUSE KEAP1_MOUSE]] Retains NFE2L2/NRF2 in the cytosol. Functions as substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1. Targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. May also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome (By similarity).<ref>PMID:9887101</ref> <ref>PMID:12682069</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Engel, C K]]
	[[Category: Loenze, P]]		[[Category: Loenze, P]]
-	[[Category: Engel, C.K]]
	[[Category: Schimanski-Breves, S]]		[[Category: Schimanski-Breves, S]]
		+	[[Category: Beta propeller]]
		+	[[Category: Complex]]
		+	[[Category: Inhibitor]]
		+	[[Category: Protein binding]]

OCA at 13:07, 12 August 2015

OCA — Wed, 12 Aug 2015 13:07:29 GMT

←Older revision		Revision as of 13:07, 12 August 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5cgj is ON HOLD	+	The entry 5cgj is ON HOLD until Jul 09 2017

	Authors: Schimanski-Breves, S., Loenze, P., Engel, C.K.		Authors: Schimanski-Breves, S., Loenze, P., Engel, C.K.

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

OCA — Wed, 15 Jul 2015 12:33:34 GMT

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

←Older revision

Revision as of 12:33, 15 July 2015

OCA: New page: '''Unreleased structure''' The entry 5cgj is ON HOLD Authors: Schimanski-Breves, S., Loenze, P., Engel, C.K. Description: Crystal structure of murine Keap1 in complex with RA839, a non...

OCA — Wed, 15 Jul 2015 12:33:33 GMT

New page: '''Unreleased structure''' The entry 5cgj is ON HOLD Authors: Schimanski-Breves, S., Loenze, P., Engel, C.K. Description: Crystal structure of murine Keap1 in complex with RA839, a non...

New page

'''Unreleased structure'''

The entry 5cgj is ON HOLD

Authors: Schimanski-Breves, S., Loenze, P., Engel, C.K.

Description: Crystal structure of murine Keap1 in complex with RA839, a non-covalent small-molecule binder to Keap1 and selective activator of Nrf2 signalling.
[[Category: Unreleased Structures]]
[[Category: Loenze, P]]
[[Category: Engel, C.K]]
[[Category: Schimanski-Breves, S]]