7jh2 - Revision history

OCA at 15:02, 18 October 2023

OCA — Wed, 18 Oct 2023 15:02:40 GMT

←Older revision		Revision as of 15:02, 18 October 2023
Line 3:		Line 3:
	<StructureSection load='7jh2' size='340' side='right'caption='[[7jh2]], [[Resolution\|resolution]] 2.37Å' scene=''>		<StructureSection load='7jh2' size='340' side='right'caption='[[7jh2]], [[Resolution\|resolution]] 2.37Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7jh2]] 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=7JH2 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=7JH2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7jh2]] 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=7JH2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JH2 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VBG:2-({[2-(4-{(3R)-1-(4-acetylpiperazine-1-carbonyl)-3-[(4-fluorophenyl)sulfonyl]pyrrolidin-3-yl}phenyl)-1,1,1,3,3,3-hexafluoropropan-2-yl]oxy}methyl)-3-fluorobenzonitrile'>VBG</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]] 2.367Å</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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VBG:2-({[2-(4-{(3R)-1-(4-acetylpiperazine-1-carbonyl)-3-[(4-fluorophenyl)sulfonyl]pyrrolidin-3-yl}phenyl)-1,1,1,3,3,3-hexafluoropropan-2-yl]oxy}methyl)-3-fluorobenzonitrile'>VBG</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=7jh2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jh2 OCA], [~~http~~://pdbe.org/7jh2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7jh2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7jh2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7jh2 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=7jh2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jh2 OCA], [https://pdbe.org/7jh2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jh2 RCSB], [https://www.ebi.ac.uk/pdbsum/7jh2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jh2 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: Sack~~, J S]]~~	+	[[Category: Sack JS]]
-	~~[[Category: Inverse agonist]]~~	+
-	~~[[Category: Ligand-binding domain]]~~	+
-	~~[[Category: Nuclear hormone receptor]]~~	+
-	~~[[Category: Rorgt]]~~	+
-	~~[[Category: Transcription-agonist complex~~]]	+

OCA at 06:43, 19 August 2020

OCA — Wed, 19 Aug 2020 06:43:57 GMT

←Older revision		Revision as of 06:43, 19 August 2020
Line 1:		Line 1:

	==CRYSTAL STRUCTURE OF RAR-RELATED ORPHAN RECEPTOR C IN COMPLEX WITH A POTENT, SELECTIVE AND ORALLY BIOAVAILABLE ROR-GAMMA-T INVERSE AGONIST==		==CRYSTAL STRUCTURE OF RAR-RELATED ORPHAN RECEPTOR C IN COMPLEX WITH A POTENT, SELECTIVE AND ORALLY BIOAVAILABLE ROR-GAMMA-T INVERSE AGONIST==
-	<StructureSection load='7jh2' size='340' side='right'caption='[[7jh2]]' scene=''>	+	<StructureSection load='7jh2' size='340' side='right'caption='[[7jh2]], [[Resolution\|resolution]] 2.37Å' 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=7JH2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7JH2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7jh2]] 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=7JH2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7JH2 FirstGlance]. <br>
-	</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=7jh2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jh2 OCA], [http://pdbe.org/7jh2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7jh2 RCSB], [http://www.ebi.ac.uk/pdbsum/7jh2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7jh2 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VBG:2-({[2-(4-{(3R)-1-(4-acetylpiperazine-1-carbonyl)-3-[(4-fluorophenyl)sulfonyl]pyrrolidin-3-yl}phenyl)-1,1,1,3,3,3-hexafluoropropan-2-yl]oxy}methyl)-3-fluorobenzonitrile'>VBG</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://proteopedia.org/fgij/fg.htm?mol=7jh2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jh2 OCA], [http://pdbe.org/7jh2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7jh2 RCSB], [http://www.ebi.ac.uk/pdbsum/7jh2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7jh2 ProSAT]</span></td></tr>
	</table>		</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 ==
		+	In an effort to discover oral inverse agonists of RORgammat to treat inflammatory diseases, a new 2,6-difluorobenzyl ether series of cyclopentyl sulfones were found to be surprisingly more potent than the corresponding alcohol derivatives. When combined with a more optimized phenyl ((R)-3-phenylpyrrolidin-3-yl)sulfone template, the 2,6-difluorobenzyl ethers yielded a set of very potent RORgammat inverse agonists (e.g., compound 26, RORgammat Gal4 EC50 11 nM) that are highly selective against PXR, LXRalpha and LXRbeta. After optimizing for stability in human and mouse liver microsomes, compounds 29 and 38 were evaluated in vivo and found to have good oral bioavailability (56% and 101%, respectively) in mice. X-ray co-crystal structure of compound 27 in RORgammat revealed that the bulky benzyl ether group causes helix 11 of the protein to partially uncoil to create a new, enlarged binding site, which nicely accommodates the benzyl ether moiety, leading to net potency gain.
		+
		+	Discovery of 2,6-difluorobenzyl ether series of phenyl ((R)-3-phenylpyrrolidin-3-yl)sulfones as surprisingly potent, selective and orally bioavailable RORgammat inverse agonists.,Duan JJ, Jiang B, Lu Z, Stachura S, Weigelt CA, Sack JS, Khan J, Ruzanov M, Wu DR, Yarde M, Shen DR, Zhao Q, Salter-Cid LM, Carter PH, Murali Dhar TG Bioorg Med Chem Lett. 2020 Jul 29;30(19):127441. doi: 10.1016/j.bmcl.2020.127441. PMID:32736080<ref>PMID:32736080</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7jh2" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Sack JS]]	+	[[Category: Sack, J S]]
		+	[[Category: Inverse agonist]]
		+	[[Category: Ligand-binding domain]]
		+	[[Category: Nuclear hormone receptor]]
		+	[[Category: Rorgt]]
		+	[[Category: Transcription-agonist complex]]

OCA at 09:51, 12 August 2020

OCA — Wed, 12 Aug 2020 09:51:08 GMT

←Older revision		Revision as of 09:51, 12 August 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7jh2 is ON HOLD~~	+	==CRYSTAL STRUCTURE OF RAR-RELATED ORPHAN RECEPTOR C IN COMPLEX WITH A POTENT, SELECTIVE AND ORALLY BIOAVAILABLE ROR-GAMMA-T INVERSE AGONIST==
-		+	<StructureSection load='7jh2' size='340' side='right'caption='[[7jh2]]' scene=''>
-	~~Authors: Sack, J.S.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JH2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7JH2 FirstGlance]. <br>
-	~~Description:~~ CRYSTAL STRUCTURE OF RAR-RELATED ORPHAN RECEPTOR C IN WITH A POTENT, SELECTIVE AND ORALLY BIOAVAILABLE ROR-GAMMA-T INVERSE AGONIST	+	</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=7jh2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jh2 OCA], [http://pdbe.org/7jh2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7jh2 RCSB], [http://www.ebi.ac.uk/pdbsum/7jh2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7jh2 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Sack~~, J.S~~]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Sack JS]]

OCA: Protected "7jh2" [edit=sysop:move=sysop]

OCA — Wed, 29 Jul 2020 09:48:21 GMT

Protected "7jh2" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:48, 29 July 2020

OCA: New page: '''Unreleased structure''' The entry 7jh2 is ON HOLD Authors: Sack, J.S. Description: CRYSTAL STRUCTURE OF RAR-RELATED ORPHAN RECEPTOR C IN WITH A POTENT, SELECTIVE AND ORALLY BIOAVAIL...

OCA — Wed, 29 Jul 2020 09:48:20 GMT

New page: '''Unreleased structure''' The entry 7jh2 is ON HOLD Authors: Sack, J.S. Description: CRYSTAL STRUCTURE OF RAR-RELATED ORPHAN RECEPTOR C IN WITH A POTENT, SELECTIVE AND ORALLY BIOAVAIL...

New page

'''Unreleased structure'''

The entry 7jh2 is ON HOLD

Authors: Sack, J.S.

Description: CRYSTAL STRUCTURE OF RAR-RELATED ORPHAN RECEPTOR C IN WITH A POTENT, SELECTIVE AND ORALLY BIOAVAILABLE ROR-GAMMA-T INVERSE AGONIST
[[Category: Unreleased Structures]]
[[Category: Sack, J.S]]