4wqp
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of RORc in complex with a benzyl sulfonamide inverse agonist== | |
| + | <StructureSection load='4wqp' size='340' side='right'caption='[[4wqp]], [[Resolution|resolution]] 1.99Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4wqp]] is a 3 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=4WQP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WQP FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.99Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3SX:N-[4-(4-ACETYLPIPERAZIN-1-YL)BENZYL]-N-(2-METHYLPROPYL)-1-PHENYLMETHANESULFONAMIDE'>3SX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4wqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wqp OCA], [https://pdbe.org/4wqp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wqp RCSB], [https://www.ebi.ac.uk/pdbsum/4wqp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wqp ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [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;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A minor structural change to tertiary sulfonamide RORc ligands led to distinct mechanisms of action. Co-crystal structures of two compounds revealed mechanistically consistent protein conformational changes. Optimized phenylsulfonamides were identified as RORc agonists while benzylsulfonamides exhibited potent inverse agonist activity. Compounds behaving as agonists in our biochemical assay also gave rise to an increased production of IL-17 in human PBMCs whereas inverse agonists led to significant suppression of IL-17 under the same assay conditions. The most potent inverse agonist compound showed >180-fold selectivity over the ROR isoforms as well as all other nuclear receptors that were profiled. | ||
| - | + | Minor Structural Change to Tertiary Sulfonamide RORc Ligands Led to Opposite Mechanisms of Action.,Rene O, Fauber BP, Boenig Gde L, Burton B, Eidenschenk C, Everett C, Gobbi A, Hymowitz SG, Johnson AR, Kiefer JR, Liimatta M, Lockey P, Norman M, Ouyang W, Wallweber HA, Wong H ACS Med Chem Lett. 2014 Dec 4;6(3):276-81. doi: 10.1021/ml500420y. eCollection, 2015 Mar 12. PMID:25815138<ref>PMID:25815138</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 4wqp" style="background-color:#fffaf0;"></div> |
| - | [[Category: Boenig | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Boenig G]] | ||
| + | [[Category: Hymowitz SG]] | ||
Current revision
Crystal structure of RORc in complex with a benzyl sulfonamide inverse agonist
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