5x8q
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structure of the mutant Human ROR gamma Ligand Binding Domain With rockogenin.== | |
| + | <StructureSection load='5x8q' size='340' side='right' caption='[[5x8q]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5x8q]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X8Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5X8Q FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=82R:(1R,2S,4S,5R,6R,7S,8R,9S,10R,12S,13S,16S,18S)-5,7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icosane-6,2-oxane]-10,16-diol'>82R</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5x8x|5x8x]], [[5x8w|5x8w]], [[5x8u|5x8u]], [[5x8s|5x8s]]</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=5x8q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x8q OCA], [http://pdbe.org/5x8q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x8q RCSB], [http://www.ebi.ac.uk/pdbsum/5x8q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x8q 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. [[http://www.uniprot.org/uniprot/NCOR2_HUMAN NCOR2_HUMAN]] Transcriptional corepressor of NR4A2/NURR1 and acts through histone deacetylases (HDACs) to keep promoters of NR4A2/NURR1 target genes in a repressed deacetylated state (By similarity). Mediates the transcriptional repression activity of some nuclear receptors by promoting chromatin condensation, thus preventing access of the basal transcription. Isoform 1 and isoform 5 have different affinities for different nuclear receptors. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Retinoid-related orphan receptor gamma (RORgamma) directly controls the differentiation of Th17 cell and the production of interleukin-17, which plays an integral role in autoimmune diseases. To obtain insight into RORgamma, we have determined the first crystal structure of a ternary complex containing RORgamma ligand-binding domain (LBD) bound with a novel synthetic inhibitor and a repressor peptide, 22-mer peptide from silencing mediator of retinoic acid and thyroid hormone receptor (SMRT). Comparison of a binary complex of nonliganded (apo) RORgamma-LBD with a nuclear receptor co-activator (NCoA-1) peptide has shown that our inhibitor displays a unique mechanism different from those caused by natural inhibitor, ursolic acid (UA). The compound unprecedentedly induces indirect disruption of a hydrogen bond between His479 on helix 11 (H11) and Tyr502 on H12, which is crucial for active conformation. This crystallographic study will allow us to develop novel synthetic compounds for autoimmune disease therapy. | ||
| - | + | Ternary complex of human RORgamma ligand-binding domain, inverse agonist and SMRT peptide shows a unique mechanism of corepressor recruitment.,Noguchi M, Nomura A, Murase K, Doi S, Yamaguchi K, Hirata K, Shiozaki M, Hirashima S, Kotoku M, Yamaguchi T, Katsuda Y, Steensma R, Li X, Tao H, Tse B, Fenn M, Babine R, Bradley E, Crowe P, Thacher S, Adachi T, Kamada M Genes Cells. 2017 Jun;22(6):535-551. doi: 10.1111/gtc.12494. Epub 2017 May 11. PMID:28493531<ref>PMID:28493531</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5x8q" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Adachi, T]] | ||
| + | [[Category: Doi, S]] | ||
| + | [[Category: Murase, K]] | ||
| + | [[Category: Noguchi, M]] | ||
| + | [[Category: Nomura, A]] | ||
| + | [[Category: Yamaguchi, K]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Nuclear receptor]] | ||
| + | [[Category: Ternary complex]] | ||
| + | [[Category: Transferase-ihibitor complex]] | ||
Revision as of 09:40, 3 August 2017
Crystal Structure of the mutant Human ROR gamma Ligand Binding Domain With rockogenin.
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