5dad - Revision history

OCA at 08:44, 27 September 2023

2023-09-27T08:44:48Z

←Older revision		Revision as of 08:44, 27 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5dad]] 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=5DAD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DAD FirstGlance]. <br>		<table><tr><td colspan='2'>[[5dad]] 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=5DAD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DAD FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TX6:(6AS,7S,10AS)-8-HYDROXY-4-METHOXY-2,7,10A-TRIMETHYL-5,6,6A,7,10,10A-HEXAHYDROBENZO[H]QUINAZOLINE-9-CARBONITRILE'>TX6</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]] 2.61Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TX6:(6AS,7S,10AS)-8-HYDROXY-4-METHOXY-2,7,10A-TRIMETHYL-5,6,6A,7,10,10A-HEXAHYDROBENZO[H]QUINAZOLINE-9-CARBONITRILE'>TX6</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=5dad FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dad OCA], [https://pdbe.org/5dad PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dad RCSB], [https://www.ebi.ac.uk/pdbsum/5dad PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dad 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=5dad FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dad OCA], [https://pdbe.org/5dad PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dad RCSB], [https://www.ebi.ac.uk/pdbsum/5dad PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dad ProSAT]</span></td></tr>
	</table>		</table>

OCA at 10:28, 21 June 2023

2023-06-21T10:28:02Z

←Older revision		Revision as of 10:28, 21 June 2023
Line 1:		Line 1:

	==Crystal Structure of Human KEAP1 BTB Domain in Complex with Small Molecule TX64014==		==Crystal Structure of Human KEAP1 BTB Domain in Complex with Small Molecule TX64014==
-	<StructureSection load='5dad' size='340' side='right' caption='[[5dad]], [[Resolution\|resolution]] 2.61Å' scene=''>	+	<StructureSection load='5dad' size='340' side='right'caption='[[5dad]], [[Resolution\|resolution]] 2.61Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5dad]] 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=5DAD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5DAD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5dad]] 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=5DAD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DAD FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TX6:(6AS,7S,10AS)-8-HYDROXY-4-METHOXY-2,7,10A-TRIMETHYL-5,6,6A,7,10,10A-HEXAHYDROBENZO[H]QUINAZOLINE-9-CARBONITRILE'>TX6</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TX6:(6AS,7S,10AS)-8-HYDROXY-4-METHOXY-2,7,10A-TRIMETHYL-5,6,6A,7,10,10A-HEXAHYDROBENZO[H]QUINAZOLINE-9-CARBONITRILE'>TX6</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5daf\|5daf]]</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=5dad FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dad OCA], [https://pdbe.org/5dad PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dad RCSB], [https://www.ebi.ac.uk/pdbsum/5dad PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dad 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~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5dad FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dad OCA], [~~http~~://pdbe.org/5dad PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5dad RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5dad PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5dad 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 ==
Line 18:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 5dad" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5dad" 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: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: Bender~~, C F~~]]	+	[[Category: Large Structures]]
-	[[Category: Dulubova, I]]	+	[[Category: Bender CF]]
-	[[Category: Ferguson~~, D A~~]]	+	[[Category: Dulubova I]]
-	[[Category: Huerta, C]]	+	[[Category: Ferguson DA]]
-	[[Category: Jiang, X]]	+	[[Category: Huerta C]]
-	[[Category: Probst, B]]	+	[[Category: Jiang X]]
-	[[Category: Stoll~~, V S~~]]	+	[[Category: Probst B]]
-	[[Category: Swinger~~, K K~~]]	+	[[Category: Stoll VS]]
-	[[Category: Thomas~~, P J~~]]	+	[[Category: Swinger KK]]
-	[[Category: Trevino, I]]	+	[[Category: Thomas PJ]]
-	[[Category: Visnick, M]]	+	[[Category: Trevino I]]
-	[[Category: Wigley~~, W C]]~~	+	[[Category: Visnick M]]
-	~~[[Category: Btb domain]]~~	+	[[Category: Wigley WC]]
-	~~[[Category: Cysteine modification]]~~	+
-	~~[[Category: Keap1]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Trascription regulation~~]]	+

OCA at 09:51, 22 November 2017

2017-11-22T09:51:22Z

←Older revision		Revision as of 09:51, 22 November 2017
Line 3:		Line 3:
	<StructureSection load='5dad' size='340' side='right' caption='[[5dad]], [[Resolution\|resolution]] 2.61Å' scene=''>		<StructureSection load='5dad' size='340' side='right' caption='[[5dad]], [[Resolution\|resolution]] 2.61Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5dad]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DAD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DAD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5dad]] 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=5DAD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DAD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TX6:(6AS,7S,10AS)-8-HYDROXY-4-METHOXY-2,7,10A-TRIMETHYL-5,6,6A,7,10,10A-HEXAHYDROBENZO[H]QUINAZOLINE-9-CARBONITRILE'>TX6</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TX6:(6AS,7S,10AS)-8-HYDROXY-4-METHOXY-2,7,10A-TRIMETHYL-5,6,6A,7,10,10A-HEXAHYDROBENZO[H]QUINAZOLINE-9-CARBONITRILE'>TX6</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5daf\|5daf]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5daf\|5daf]]</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5dad FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dad OCA], [http://pdbe.org/5dad PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dad RCSB], [http://www.ebi.ac.uk/pdbsum/5dad PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dad 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=5dad FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dad OCA], [http://pdbe.org/5dad PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dad RCSB], [http://www.ebi.ac.uk/pdbsum/5dad PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dad ProSAT]</span></td></tr>
	</table>		</table>
Line 21:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Bender, C F]]		[[Category: Bender, C F]]
	[[Category: Dulubova, I]]		[[Category: Dulubova, I]]

OCA at 15:49, 10 August 2016

2016-08-10T15:49:27Z

←Older revision		Revision as of 15:49, 10 August 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5dad is ~~ON HOLD until Paper~~ Publication	+	==Crystal Structure of Human KEAP1 BTB Domain in Complex with Small Molecule TX64014==
		+	<StructureSection load='5dad' size='340' side='right' caption='[[5dad]], [[Resolution\|resolution]] 2.61Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5dad]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DAD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DAD FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TX6:(6AS,7S,10AS)-8-HYDROXY-4-METHOXY-2,7,10A-TRIMETHYL-5,6,6A,7,10,10A-HEXAHYDROBENZO[H]QUINAZOLINE-9-CARBONITRILE'>TX6</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5daf\|5daf]]</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=5dad FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dad OCA], [http://pdbe.org/5dad PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dad RCSB], [http://www.ebi.ac.uk/pdbsum/5dad PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dad ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BACKGROUND: Semi-synthetic oleanane triterpenoid antioxidant inflammation modulators (tpAIMs) are small molecules that interact with KEAP1 cysteine residue 151 (C151) and activate NRF2. Exploration of the structure-activity relationship between the tpAIMs and KEAP1 is limited by the predominantly hydrocarbon nature of the oleanane triterpenoid pentacyclic ring structure. Therefore, we used novel, chemically tractable, synthetic antioxidant inflammation modulators (sAIMs) to probe the stereoselectivity of the ligand-protein interaction. METHODS: We measured several parameters of NRF2 activation to assess the potency of sAIM enantiomers with natural (tpAIM-like) 4(S),5(S),10(R) or unnatural 4(R),5(R),10(S) configurations. Additionally, we determined the crystal structure of the KEAP1 BTB domain in complex with two different sAIMs. RESULTS: We found that the potencies of sAIM enantiomers in the natural configuration were similar to those of the tpAIM, RTA 405. Strikingly, sAIM enantiomers in the unnatural configuration were 10- to 40-fold less potent than their natural counterparts. Crystallographic studies of sAIMs in complex with the KEAP1 BTB domain demonstrated that these ligands form a covalent bond with C151 and revealed the presence of additional hydrogen bonds, Van der Waals interactions, and pi-stacking interactions. CONCLUSIONS: Although KEAP1 C151 is required for NRF2 activation by tpAIMs and sAIMs, interactions with other KEAP1 residues are critical for the stereospecific recognition and potency of these ligands. GENERAL SIGNIFICANCE: This work demonstrates that reversible cyanoenone Michael acceptors, such as the tpAIMs and sAIMs, can be specifically tuned to regulate redox sensitive cysteine residues on key signaling molecules, an approach with significant promise for innovative drug development.

-	~~Authors~~: ~~Huerta~~, C., Jiang, X., Trevino, I., Bender, ~~C.F.~~, Swinger~~, K.K.~~, Stoll~~, V.S., Ferguson, D.A.~~, Thomas~~, P.J., Probst, B.~~, Dulubova, I., Visnick, M., Wigley, W.C.	+	Characterization of novel small-molecule NRF2 activators: Structural and biochemical validation of stereospecific KEAP1 binding.,Huerta C, Jiang X, Trevino I, Bender CF, Ferguson DA, Probst B, Swinger KK, Stoll VS, Thomas PJ, Dulubova I, Visnick M, Wigley WC Biochim Biophys Acta. 2016 Jul 27. pii: S0304-4165(16)30273-2. doi:, 10.1016/j.bbagen.2016.07.026. PMID:27474998<ref>PMID:27474998</ref>

-	~~Description: Crystal Structure~~ of ~~Human KEAP1 BTB Domain in Complex with Small Molecule TX64014~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	~~[[Category: Stoll, V.S]]~~	+	<div class="pdbe-citations 5dad" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Trevino~~, I]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Bender, C F]]
	[[Category: Dulubova, I]]		[[Category: Dulubova, I]]
		+	[[Category: Ferguson, D A]]
	[[Category: Huerta, C]]		[[Category: Huerta, C]]
-	[[Category: ~~Wigley~~, ~~W.C]]~~	+	[[Category: Jiang, X]]
-	~~[[Category: Thomas, P.J~~]]	+
	[[Category: Probst, B]]		[[Category: Probst, B]]
-	[[Category: Swinger, K.K]]	+	[[Category: Stoll, V S]]
-	[[Category: ~~Bender~~, ~~C.F~~]]	+	[[Category: Swinger, K K]]
		+	[[Category: Thomas, P J]]
		+	[[Category: Trevino, I]]
	[[Category: Visnick, M]]		[[Category: Visnick, M]]
-	[[Category: ~~Ferguson~~, ~~D.A~~]]	+	[[Category: Wigley, W C]]
-	[[Category: ~~Jiang, X~~]]	+	[[Category: Btb domain]]
		+	[[Category: Cysteine modification]]
		+	[[Category: Keap1]]
		+	[[Category: Transcription]]
		+	[[Category: Trascription regulation]]

OCA at 11:01, 16 December 2015

2015-12-16T11:01:54Z

←Older revision		Revision as of 11:01, 16 December 2015
Line 9:		Line 9:
	[[Category: Stoll, V.S]]		[[Category: Stoll, V.S]]
	[[Category: Trevino, I]]		[[Category: Trevino, I]]
-	[[Category: Wigley, W.C]]
-	[[Category: Swinger, K.K]]
-	[[Category: Visnick, M]]
-	[[Category: Ferguson, D.A]]
-	[[Category: Jiang, X]]
	[[Category: Dulubova, I]]		[[Category: Dulubova, I]]
	[[Category: Huerta, C]]		[[Category: Huerta, C]]
		+	[[Category: Wigley, W.C]]
	[[Category: Thomas, P.J]]		[[Category: Thomas, P.J]]
	[[Category: Probst, B]]		[[Category: Probst, B]]
		+	[[Category: Swinger, K.K]]
	[[Category: Bender, C.F]]		[[Category: Bender, C.F]]
		+	[[Category: Visnick, M]]
		+	[[Category: Ferguson, D.A]]
		+	[[Category: Jiang, X]]

OCA at 12:49, 30 September 2015

2015-09-30T12:49:13Z

←Older revision		Revision as of 12:49, 30 September 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5dad is ON HOLD	+	The entry 5dad is ON HOLD until Paper Publication

	Authors: Huerta, C., Jiang, X., Trevino, I., Bender, C.F., Swinger, K.K., Stoll, V.S., Ferguson, D.A., Thomas, P.J., Probst, B., Dulubova, I., Visnick, M., Wigley, W.C.		Authors: Huerta, C., Jiang, X., Trevino, I., Bender, C.F., Swinger, K.K., Stoll, V.S., Ferguson, D.A., Thomas, P.J., Probst, B., Dulubova, I., Visnick, M., Wigley, W.C.

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

2015-08-26T12:39:00Z

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

←Older revision

Revision as of 12:39, 26 August 2015

OCA: New page: '''Unreleased structure''' The entry 5dad is ON HOLD Authors: Huerta, C., Jiang, X., Trevino, I., Bender, C.F., Swinger, K.K., Stoll, V.S., Ferguson, D.A., Thomas, P.J., Probst, B., Dul...

2015-08-26T12:38:58Z

New page: '''Unreleased structure''' The entry 5dad is ON HOLD Authors: Huerta, C., Jiang, X., Trevino, I., Bender, C.F., Swinger, K.K., Stoll, V.S., Ferguson, D.A., Thomas, P.J., Probst, B., Dul...

New page

'''Unreleased structure'''

The entry 5dad is ON HOLD

Authors: Huerta, C., Jiang, X., Trevino, I., Bender, C.F., Swinger, K.K., Stoll, V.S., Ferguson, D.A., Thomas, P.J., Probst, B., Dulubova, I., Visnick, M., Wigley, W.C.

Description: Crystal Structure of Human KEAP1 BTB Domain in Complex with Small Molecule TX64014
[[Category: Unreleased Structures]]
[[Category: Stoll, V.S]]
[[Category: Trevino, I]]
[[Category: Wigley, W.C]]
[[Category: Swinger, K.K]]
[[Category: Visnick, M]]
[[Category: Ferguson, D.A]]
[[Category: Jiang, X]]
[[Category: Dulubova, I]]
[[Category: Huerta, C]]
[[Category: Thomas, P.J]]
[[Category: Probst, B]]
[[Category: Bender, C.F]]