6fgq - Revision history

OCA at 12:28, 9 May 2024

OCA — Thu, 09 May 2024 12:28:13 GMT

←Older revision		Revision as of 12:28, 9 May 2024
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	==Ligand complex of RORg LBD==		==Ligand complex of RORg LBD==
-	<StructureSection load='6fgq' size='340' side='right' caption='[[6fgq]], [[Resolution\|resolution]] 2.37Å' scene=''>	+	<StructureSection load='6fgq' size='340' side='right'caption='[[6fgq]], [[Resolution\|resolution]] 2.37Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6fgq]] 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=6FGQ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6FGQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6fgq]] 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=6FGQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FGQ FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=D9N:methyl+4~~-[[~~3-[5-[2-(4-ethylsulfonylphenyl)ethanoylamino~~]~~thiophen-3-yl~~]~~pyridin-~~2~~-yl]oxymethyl]benzoate'>D9N</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]] 2.37Å</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=D9N:methyl+4-[[3-[5-[2-(4-ethylsulfonylphenyl)ethanoylamino]thiophen-3-yl]pyridin-2-yl]oxymethyl]benzoate'>D9N</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=6fgq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fgq OCA], [~~http~~://pdbe.org/6fgq PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6fgq RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6fgq PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6fgq 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=6fgq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fgq OCA], [https://pdbe.org/6fgq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fgq RCSB], [https://www.ebi.ac.uk/pdbsum/6fgq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fgq 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 ==
Line 23:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Aagaard, A~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Narjes, F~~]]	+	[[Category: Aagaard A]]
-	[[Category: ~~Xue, Y~~]]	+	[[Category: Narjes F]]
-	[[Category: ~~Rorg ligand]]~~	+	[[Category: Xue Y]]
-	~~[[Category: Structure-based design]]~~	+
-	~~[[Category: Transcription~~]]	+

OCA at 06:56, 24 October 2018

OCA — Wed, 24 Oct 2018 06:56:42 GMT

←Older revision		Revision as of 06:56, 24 October 2018
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	<StructureSection load='6fgq' size='340' side='right' caption='[[6fgq]], [[Resolution\|resolution]] 2.37Å' scene=''>		<StructureSection load='6fgq' size='340' side='right' caption='[[6fgq]], [[Resolution\|resolution]] 2.37Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6fgq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FGQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FGQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6fgq]] 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=6FGQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FGQ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=D9N:methyl+4-[[3-[5-[2-(4-ethylsulfonylphenyl)ethanoylamino]thiophen-3-yl]pyridin-2-yl]oxymethyl]benzoate'>D9N</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=D9N:methyl+4-[[3-[5-[2-(4-ethylsulfonylphenyl)ethanoylamino]thiophen-3-yl]pyridin-2-yl]oxymethyl]benzoate'>D9N</scene></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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6fgq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fgq OCA], [http://pdbe.org/6fgq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fgq RCSB], [http://www.ebi.ac.uk/pdbsum/6fgq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fgq 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=6fgq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fgq OCA], [http://pdbe.org/6fgq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fgq RCSB], [http://www.ebi.ac.uk/pdbsum/6fgq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fgq ProSAT]</span></td></tr>
	</table>		</table>
Line 22:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Aagaard, A]]		[[Category: Aagaard, A]]
	[[Category: Narjes, F]]		[[Category: Narjes, F]]

OCA at 06:11, 22 August 2018

OCA — Wed, 22 Aug 2018 06:11:13 GMT

←Older revision		Revision as of 06:11, 22 August 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6fgq is ~~ON HOLD until Paper~~ Publication	+	==Ligand complex of RORg LBD==
		+	<StructureSection load='6fgq' size='340' side='right' caption='[[6fgq]], [[Resolution\|resolution]] 2.37Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6fgq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FGQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FGQ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=D9N:methyl+4-[[3-[5-[2-(4-ethylsulfonylphenyl)ethanoylamino]thiophen-3-yl]pyridin-2-yl]oxymethyl]benzoate'>D9N</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=6fgq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fgq OCA], [http://pdbe.org/6fgq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fgq RCSB], [http://www.ebi.ac.uk/pdbsum/6fgq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fgq ProSAT]</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 ==
		+	Retinoic acid receptor-related orphan receptor gammat (RORgammat), has been identified as the master regulator of TH17 cell function and development, making it an attractive target for the treatment of autoimmune diseases by a small molecule approach. Herein we describe our investigations on a series of 4-aryl-thienyl acetamides, which were guided by insights from X-ray co-crystal structures. Efforts in targeting the co-factor recruitment site from the 4-aryl group on the thiophene led to a series of potent binders, with nanomolar activity in a primary human TH17 cell assay. The observation of a molecule of DMSO binding in a sub-pocket outside the LBD inspired the introduction of an acetamide into the benzylic position of these compounds. Hereby, a hydrogen bond interaction of the introduced acetamide oxygen with the backbone amide of Glu379 was established. This greatly enhanced the cellular activity of previously weakly cell active compounds. The best compounds combined potent inhibition of IL-17 release with favorable PK in rodents with compound 32 representing a promising starting point for future investigations.

-	~~Authors: Xue~~, Y., ~~Aagaard~~, A., ~~Narjes~~, F.	+	Structure-based design leads to potent and orally bioavailable inverse agonists of RORgammat.,Narjes F, Xue Y, von Berg S, Malmberg J, Llinas A, Olsson RI, Jirholt J, Grindebacke H, Leffler A, Hossain N, Lepisto M, Thunberg L, Leek H, Aagaard A, McPheat J, Hansson EL, Back E, Tangefjord S, Chen R, Xiong Y, Hongbin G, Hansson T J Med Chem. 2018 Aug 10. doi: 10.1021/acs.jmedchem.8b00783. PMID:30095900<ref>PMID:30095900</ref>

-	~~Description: Ligand complex~~ of ~~RORg LBD~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
		+	<div class="pdbe-citations 6fgq" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Aagaard, A]]		[[Category: Aagaard, A]]
-	[[Category: Xue, Y]]
	[[Category: Narjes, F]]		[[Category: Narjes, F]]
		+	[[Category: Xue, Y]]
		+	[[Category: Rorg ligand]]
		+	[[Category: Structure-based design]]
		+	[[Category: Transcription]]

OCA: Protected "6fgq" [edit=sysop:move=sysop]

OCA — Wed, 17 Jan 2018 05:55:02 GMT

Protected "6fgq" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:55, 17 January 2018

OCA: New page: '''Unreleased structure''' The entry 6fgq is ON HOLD until Paper Publication Authors: Xue, Y., Aagaard, A., Narjes, F. Description: Ligand complex of RORg LBD [[Category: Unreleased St...

OCA — Wed, 17 Jan 2018 05:55:00 GMT

New page: '''Unreleased structure''' The entry 6fgq is ON HOLD until Paper Publication Authors: Xue, Y., Aagaard, A., Narjes, F. Description: Ligand complex of RORg LBD [[Category: Unreleased St...

New page

'''Unreleased structure'''

The entry 6fgq is ON HOLD until Paper Publication

Authors: Xue, Y., Aagaard, A., Narjes, F.

Description: Ligand complex of RORg LBD
[[Category: Unreleased Structures]]
[[Category: Aagaard, A]]
[[Category: Xue, Y]]
[[Category: Narjes, F]]