5x8s | pdb_00005x8s

Crystal Structure of the mutant Human ROR gamma Ligand Binding Domain With Ursolic acid.

spinqualitylabelsall models 5x8s, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5x8s is a 2 chain structure with sequence from Hylobates concolor leucogenys. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 6Q5 Related: 5x8x, 5x8u, 5x8w, 5x8q Gene: RORC, NR1F3, RORG, RZRG (Hylobates concolor leucogenys) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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