4qm0
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4qm0]] 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=4QM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QM0 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4qm0]] 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=4QM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QM0 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=39K:N-(2-METHYLPROPYL)-N-({5-[4-(METHYLSULFONYL)PHENYL]THIOPHEN-2-YL}METHYL)-1-PHENYLMETHANESULFONAMIDE'>39K</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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]] 2.195Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=39K:N-(2-METHYLPROPYL)-N-({5-[4-(METHYLSULFONYL)PHENYL]THIOPHEN-2-YL}METHYL)-1-PHENYLMETHANESULFONAMIDE'>39K</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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=4qm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qm0 OCA], [https://pdbe.org/4qm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qm0 RCSB], [https://www.ebi.ac.uk/pdbsum/4qm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qm0 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=4qm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qm0 OCA], [https://pdbe.org/4qm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qm0 RCSB], [https://www.ebi.ac.uk/pdbsum/4qm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qm0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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. | [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 == | ||
| - | Using structure-based drug design principles, we identified opportunities to reduce the lipophilicity of our tertiary sulfonamide RORc inverse agonists. The new analogs possessed improved RORc cellular potencies with >77-fold selectivity for RORc over other nuclear receptors in our cell assay suite. The reduction in lipophilicity also led to an increased plasma-protein unbound fraction and improvements in cellular permeability and aqueous solubility. | ||
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| - | Reduction in lipophilicity improved the solubility, plasma-protein binding, and permeability of tertiary sulfonamide RORc inverse agonists.,Fauber BP, Rene O, de Leon Boenig G, Burton B, Deng Y, Eidenschenk C, Everett C, Gobbi A, Hymowitz SG, Johnson AR, La H, Liimatta M, Lockey P, Norman M, Ouyang W, Wang W, Wong H Bioorg Med Chem Lett. 2014 Aug 15;24(16):3891-7. doi: 10.1016/j.bmcl.2014.06.048., Epub 2014 Jun 25. PMID:25017032<ref>PMID:25017032</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4qm0" style="background-color:#fffaf0;"></div> | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Crystal structure of RORc in complex with a tertiary sulfonamide inverse agonist
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