5za1
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Ligand complex of RORgt LBD== | |
| + | <StructureSection load='5za1' size='340' side='right' caption='[[5za1]], [[Resolution|resolution]] 2.52Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5za1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZA1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZA1 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9A0:2-[4-({[4-(ethylsulfonyl)phenyl]acetyl}amino)phenyl]-2-methyl-N-phenylpropanamide'>9A0</scene>, <scene name='pdbligand=DMF:DIMETHYLFORMAMIDE'>DMF</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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=5za1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5za1 OCA], [http://pdbe.org/5za1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5za1 RCSB], [http://www.ebi.ac.uk/pdbsum/5za1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5za1 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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The retinoic acid receptor-related orphan receptor-gamma-t (RORgammat) is the master transcription factor responsible for regulating the development and function of T-helper 17 (Th17) cells, which are related to the pathology of several autoimmune disorders. Therefore, RORgammat is an attractive drug target for such Th17-mediated autoimmune diseases. A structure-activity relationship (SAR) study of lead compound 1 yielded a novel series of RORgammat inhibitors, represented by compound 6. Detailed SAR optimization, informed by X-ray cocrystal structure analysis, led to the discovery of a potent orally bioavailable RORgammat inhibitor 25, which inhibited IL-17 production in the skin of IL-23-treated mice by oral administration. | ||
| - | + | Discovery of a potent orally bioavailable retinoic acid receptor-related orphan receptor-gamma-t (RORgammat) inhibitor, S18-000003.,Sasaki Y, Odan M, Yamamoto S, Kida S, Ueyama A, Shimizu M, Haruna T, Watanabe A, Okuno T Bioorg Med Chem Lett. 2018 Dec 1;28(22):3549-3553. doi:, 10.1016/j.bmcl.2018.09.032. Epub 2018 Sep 27. PMID:30301676<ref>PMID:30301676</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 5za1" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Yamaguchi, H]] | [[Category: Yamaguchi, H]] | ||
[[Category: Yamamoto, S]] | [[Category: Yamamoto, S]] | ||
| + | [[Category: Rorgt inhibitor]] | ||
| + | [[Category: Rorgt ligand]] | ||
| + | [[Category: Structure-based design]] | ||
| + | [[Category: Transcription]] | ||
Revision as of 06:45, 31 October 2018
Ligand complex of RORgt LBD
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