6g07: Difference between revisions

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-'''Unreleased structure'''
-The entry 6g07 is ON HOLD  until Paper Publication
+==RORGT (264-518;C455S) IN COMPLEX WITH INVERSE AGONIST "CPD-9" AND RIP140 PEPTIDE AT 1.66A==
+<StructureSection load='6g07' size='340' side='right' caption='[[6g07]], [[Resolution|resolution]] 1.66&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6g07]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G07 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G07 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EEZ:~{N}-[5-chloranyl-6-[(1~{S})-1-phenylethoxy]pyridin-3-yl]-2-(4-ethylsulfonylphenyl)ethanamide'>EEZ</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6fzu|6fzu]], [[6g05|6g05]]</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=6g07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g07 OCA], [http://pdbe.org/6g07 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g07 RCSB], [http://www.ebi.ac.uk/pdbsum/6g07 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g07 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. [[http://www.uniprot.org/uniprot/NRIP1_HUMAN NRIP1_HUMAN]] Modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1. Also modulates transcriptional repression by nuclear hormone receptors.<ref>PMID:7641693</ref> <ref>PMID:10364267</ref> <ref>PMID:11509661</ref> <ref>PMID:11518808</ref> <ref>PMID:12554755</ref> <ref>PMID:15060175</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The transcription factor RORgammat is an attractive drug-target due to its role in the differentiation of IL-17 producing Th17 cells that play a critical role in the etiopathology of several autoimmune diseases. Identification of starting points for RORgammat inverse agonists with good properties has been a challenge. We report the identification of a fragment hit and its conversion into a potent inverse agonist through fragment optimization, growing and merging efforts. Further analysis of the binding mode revealed that inverse agonism was achieved by an unusual mechanism. In contrast to other reported inverse agonists, there is no direct interaction or displacement of helix 12 observed in the crystal structure. Nevertheless, compound 9 proved to be efficacious in a delayed-type hypersensitivity (DTH) inflammation model in rats.
-Authors: Kallen, J.
+Optimizing a weakly binding fragment into a potent RORgammat inverse agonist with efficacy in an in vivo inflammation model.,Carcache D, Vulpetti A, Kallen J, Mattes H, Orain D, Stringer R, Vangrevelinghe E, Wolf RM, Kaupmann K, Ottl J, Dawson King J, Cooke NG, Hoegenauer K, Billich A, Wagner J, Guntermann C, Hintermann S J Med Chem. 2018 Jul 10. doi: 10.1021/acs.jmedchem.8b00529. PMID:29990434<ref>PMID:29990434</ref>
-Description: RORGT (264-518;C455S) IN COMPLEX WITH INVERSE AGONIST ""CPD-9"" AND RIP140 PEPTIDE AT 1.66A
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6g07" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Kallen, J]]
+[[Category: Fb]]
+[[Category: Inverse agonist]]
+[[Category: Ligand binding domain]]
+[[Category: Nuclear hormone receptor]]
+[[Category: Transcription]]