6a22: Difference between revisions

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-'''Unreleased structure'''
-The entry 6a22 is ON HOLD
+==Ternary complex of Human ROR gamma Ligand Binding Domain With Compound T.==
+<StructureSection load='6a22' size='340' side='right'caption='[[6a22]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6a22]] is a 8 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=6A22 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6A22 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]] 2.55&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9P6:2-[2-[1-~{tert}-butyl-5-(4-methoxyphenyl)pyrazol-4-yl]-1,3-thiazol-4-yl]-~{N}-(oxan-4-ylmethyl)ethanamide'>9P6</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=6a22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a22 OCA], [https://pdbe.org/6a22 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6a22 RCSB], [https://www.ebi.ac.uk/pdbsum/6a22 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6a22 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 ==
+Retinoic acid-related orphan receptor gamma (RORgamma) plays pivotal roles in autoimmune diseases by controlling the lineage of interleukin 17 (IL-17)-producing CD4(+) T cells (Th17 cells). Structure-based drug design has proven fruitful in the development of inhibitors targeting the ligand binding domain (LBD) of RORgamma. Here, we present the crystal structure of a novel RORgamma inhibitor co-complex, in the presence of a corepressor (CoR) peptide. This ternary complex with compound T reveals the structural basis for an inhibitory mechanism different from the previously reported inverse agonist. Compared to the inverse agonist, compound T induces about 2 A shift of helix 5 (H5) backbone and side-chain conformational changes of Met365 on H5. These conformational changes correlate to reduced CoR peptide binding to RORgamma-LBD in the presence of compound T, which suggests that the shift of H5 is responsible. This crystal structure analysis will provide useful information for the development of novel and efficacious drugs for autoimmune disorders.
-Authors:
+Ternary crystal structure of human RORgamma ligand-binding-domain, an inhibitor and corepressor peptide provides a new insight into corepressor interaction.,Noguchi M, Nomura A, Doi S, Yamaguchi K, Hirata K, Shiozaki M, Maeda K, Hirashima S, Kotoku M, Yamaguchi T, Katsuda Y, Crowe P, Tao H, Thacher S, Adachi T Sci Rep. 2018 Nov 26;8(1):17374. doi: 10.1038/s41598-018-35783-9. PMID:30478402<ref>PMID:30478402</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6a22" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Nuclear receptor corepressor|Nuclear receptor corepressor]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Adachi T]]
+[[Category: Doi S]]
+[[Category: Noguchi M]]
+[[Category: Nomura A]]
+[[Category: Yamaguchi K]]