5iz0 - Revision history

OCA at 10:39, 6 September 2023

2023-09-06T10:39:29Z

←Older revision		Revision as of 10:39, 6 September 2023
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	<StructureSection load='5iz0' size='340' side='right'caption='[[5iz0]], [[Resolution\|resolution]] 2.63Å' scene=''>		<StructureSection load='5iz0' size='340' side='right'caption='[[5iz0]], [[Resolution\|resolution]] 2.63Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5iz0]] is a 8 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=5IZ0 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5IZ0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5iz0]] is a 8 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=5IZ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IZ0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6F1:N-(4-ETHYL-3-OXO-3,4-DIHYDRO-2H-1,4-BENZOXAZIN-7-YL)-3,4-DIMETHYL-N-(2,2,2-TRIFLUOROETHYL)BENZENE-1-SULFONAMIDE'>6F1</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 2.635Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">RORC, NR1F3, RORG, RZRG ([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=6F1:N-(4-ETHYL-3-OXO-3,4-DIHYDRO-2H-1,4-BENZOXAZIN-7-YL)-3,4-DIMETHYL-N-(2,2,2-TRIFLUOROETHYL)BENZENE-1-SULFONAMIDE'>6F1</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=5iz0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iz0 OCA], [~~http~~://pdbe.org/5iz0 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5iz0 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5iz0 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5iz0 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=5iz0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iz0 OCA], [https://pdbe.org/5iz0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5iz0 RCSB], [https://www.ebi.ac.uk/pdbsum/5iz0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5iz0 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/RORG_HUMAN RORG_HUMAN]] Possible nuclear receptor for hydroxycholesterols, the binding of which strongly promotes coactivators recruitment. Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes. Involved in lineage specification of uncommitted CD4(+) T-helper cells into Th17 cells. Regulate the expression of several components of the circadian clock.	+	[https://www.uniprot.org/uniprot/RORG_HUMAN RORG_HUMAN] Possible nuclear receptor for hydroxycholesterols, the binding of which strongly promotes coactivators recruitment. Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes. Involved in lineage specification of uncommitted CD4(+) T-helper cells into Th17 cells. Regulate the expression of several components of the circadian clock.
	<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: Marcotte~~, D J]]~~	+	[[Category: Marcotte DJ]]
-	~~[[Category: Af2 helix]]~~	+
-	~~[[Category: Agonist]]~~	+
-	~~[[Category: Immune system]]~~	+
-	~~[[Category: Nuclear hormone receptor]]~~	+
-	~~[[Category: Rorgamma~~]]	+

OCA at 07:22, 10 June 2020

2020-06-10T07:22:13Z

←Older revision		Revision as of 07:22, 10 June 2020
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	==RORgamma in complex with agonist BIO592 and Coactivator EBI96==		==RORgamma in complex with agonist BIO592 and Coactivator EBI96==
-	<StructureSection load='5iz0' size='340' side='right' caption='[[5iz0]], [[Resolution\|resolution]] 2.63Å' scene=''>	+	<StructureSection load='5iz0' size='340' side='right'caption='[[5iz0]], [[Resolution\|resolution]] 2.63Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5iz0]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IZ0 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5IZ0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5iz0]] is a 8 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=5IZ0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5IZ0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6F1:N-(4-ETHYL-3-OXO-3,4-DIHYDRO-2H-1,4-BENZOXAZIN-7-YL)-3,4-DIMETHYL-N-(2,2,2-TRIFLUOROETHYL)BENZENE-1-SULFONAMIDE'>6F1</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6F1:N-(4-ETHYL-3-OXO-3,4-DIHYDRO-2H-1,4-BENZOXAZIN-7-YL)-3,4-DIMETHYL-N-(2,2,2-TRIFLUOROETHYL)BENZENE-1-SULFONAMIDE'>6F1</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=5iz0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iz0 OCA], [http://pdbe.org/5iz0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5iz0 RCSB], [http://www.ebi.ac.uk/pdbsum/5iz0 PDBsum]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">RORC, NR1F3, RORG, RZRG ([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=5iz0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iz0 OCA], [http://pdbe.org/5iz0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5iz0 RCSB], [http://www.ebi.ac.uk/pdbsum/5iz0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5iz0 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 22:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Marcotte, D J]]		[[Category: Marcotte, D J]]
	[[Category: Af2 helix]]		[[Category: Af2 helix]]

OCA at 15:11, 20 June 2016

2016-06-20T15:11:30Z

←Older revision		Revision as of 15:11, 20 June 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5iz0 is ~~ON HOLD~~	+	==RORgamma in complex with agonist BIO592 and Coactivator EBI96==
		+	<StructureSection load='5iz0' size='340' side='right' caption='[[5iz0]], [[Resolution\|resolution]] 2.63Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5iz0]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IZ0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IZ0 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6F1:N-(4-ETHYL-3-OXO-3,4-DIHYDRO-2H-1,4-BENZOXAZIN-7-YL)-3,4-DIMETHYL-N-(2,2,2-TRIFLUOROETHYL)BENZENE-1-SULFONAMIDE'>6F1</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=5iz0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iz0 OCA], [http://pdbe.org/5iz0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5iz0 RCSB], [http://www.ebi.ac.uk/pdbsum/5iz0 PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/RORG_HUMAN RORG_HUMAN]] Possible nuclear receptor for hydroxycholesterols, the binding of which strongly promotes coactivators recruitment. Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes. Involved in lineage specification of uncommitted CD4(+) T-helper cells into Th17 cells. Regulate the expression of several components of the circadian clock.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BACKGROUND: The nuclear hormone receptor RORgamma regulates transcriptional genes involved in the production of the pro-inflammatory interleukin IL-17 which has been linked to autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. This transcriptional activity of RORgamma is modulated through a protein-protein interaction involving the activation function 2 (AF2) helix on the ligand binding domain of RORgamma and a conserved LXXLL helix motif on coactivator proteins. Our goal was to develop a RORgamma specific inverse agonist that would help down regulate pro-inflammatory gene transcription by disrupting the protein protein interaction with coactivator proteins as a therapeutic agent. RESULTS: We identified a novel series of synthetic benzoxazinone ligands having an agonist (BIO592) and inverse agonist (BIO399) mode of action in a FRET based assay. We show that the AF2 helix of RORgamma is proteolytically sensitive when inverse agonist BIO399 binds. Using x-ray crystallography we show how small modifications on the benzoxazinone agonist BIO592 trigger inverse agonism of RORgamma. Using an in vivo reporter assay, we show that the inverse agonist BIO399 displayed specificity for RORgamma over ROR sub-family members alpha and beta. CONCLUSION: The synthetic benzoxazinone ligands identified in our FRET assay have an agonist (BIO592) or inverse agonist (BIO399) effect by stabilizing or destabilizing the agonist conformation of RORgamma. The proteolytic sensitivity of the AF2 helix of RORgamma demonstrates that it destabilizes upon BIO399 inverse agonist binding perturbing the coactivator protein binding site. Our structural investigation of the BIO592 agonist and BIO399 inverse agonist structures identified residue Met358 on RORgamma as the trigger for RORgamma specific inverse agonism.

-	~~Authors:~~ Marcotte, D.J.	+	Structural determinant for inducing RORgamma specific inverse agonism triggered by a synthetic benzoxazinone ligand.,Marcotte DJ, Liu Y, Little K, Jones JH, Powell NA, Wildes CP, Silvian LF, Chodaparambil JV BMC Struct Biol. 2016 Jun 1;16(1):7. doi: 10.1186/s12900-016-0059-3. PMID:27246200<ref>PMID:27246200</ref>

-	~~Description~~: ~~RORgamma in complex with agonist BIO592 and Coactivator EBI96~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Marcotte, D.J~~]]	+	<div class="pdbe-citations 5iz0" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Marcotte, D J]]
		+	[[Category: Af2 helix]]
		+	[[Category: Agonist]]
		+	[[Category: Immune system]]
		+	[[Category: Nuclear hormone receptor]]
		+	[[Category: Rorgamma]]

OCA: Protected "5iz0" [edit=sysop:move=sysop]

2016-05-11T01:11:23Z

Protected "5iz0" [edit=sysop:move=sysop]

←Older revision

Revision as of 01:11, 11 May 2016

OCA: New page: '''Unreleased structure''' The entry 5iz0 is ON HOLD Authors: Marcotte, D.J. Description: RORgamma in complex with agonist BIO592 and Coactivator EBI96 [[Category: Unreleased Structure...

2016-05-11T01:11:21Z

New page: '''Unreleased structure''' The entry 5iz0 is ON HOLD Authors: Marcotte, D.J. Description: RORgamma in complex with agonist BIO592 and Coactivator EBI96 [[Category: Unreleased Structure...

New page

'''Unreleased structure'''

The entry 5iz0 is ON HOLD

Authors: Marcotte, D.J.

Description: RORgamma in complex with agonist BIO592 and Coactivator EBI96
[[Category: Unreleased Structures]]
[[Category: Marcotte, D.J]]