5X8U
Crystal Structure of the wild Human ROR gamma Ligand Binding Domain.
Summary for 5X8U
| Entry DOI | 10.2210/pdb5x8u/pdb |
| Related | 5X8Q 5X8S 5X8W 5X8X |
| Descriptor | Nuclear receptor ROR-gamma, Nuclear receptor coactivator 1 (3 entities in total) |
| Functional Keywords | inhibitor, binary complex, nuclear receptor, transferase-inhibitor complex, transferase/inhibitor |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 31674.59 |
| Authors | Noguchi, M.,Nomura, A.,Murase, K.,Doi, S.,Yamaguchi, K.,Adachi, T. (deposition date: 2017-03-03, release date: 2017-06-07, Last modification date: 2023-11-22) |
| Primary citation | 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. Ternary complex of human ROR gamma ligand-binding domain, inverse agonist and SMRT peptide shows a unique mechanism of corepressor recruitment Genes Cells, 22:535-551, 2017 Cited by PubMed Abstract: Retinoid-related orphan receptor gamma (RORγ) 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 RORγ, we have determined the first crystal structure of a ternary complex containing RORγ 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) RORγ-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. PubMed: 28493531DOI: 10.1111/gtc.12494 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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