4wpf
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 4wpf is ON HOLD until Paper Publication Authors: Kiefer, J.R., Wallweber, H.A., Boenig, G., Hymowitz, S.G. Description:) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of RORc in complex with a phenyl sulfonamide agonist== | |
| + | <StructureSection load='4wpf' size='340' side='right'caption='[[4wpf]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4wpf]] is a 4 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=4WPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WPF 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]] 2.202Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3SN:N-[4-(4-ACETYLPIPERAZIN-1-YL)-2-FLUOROBENZYL]-N-CYCLOBUTYLBENZENESULFONAMIDE'>3SN</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=4wpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wpf OCA], [https://pdbe.org/4wpf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wpf RCSB], [https://www.ebi.ac.uk/pdbsum/4wpf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wpf 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> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4wpf" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Hymowitz SG]] | ||
| + | [[Category: Kiefer JR]] | ||
| + | [[Category: Wallweber HA]] | ||
| + | [[Category: De Leon Boenig G]] | ||
Current revision
Crystal structure of RORc in complex with a phenyl sulfonamide agonist
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