3H52
Crystal structure of the antagonist form of human glucocorticoid receptor
Summary for 3H52
| Entry DOI | 10.2210/pdb3h52/pdb |
| Descriptor | Glucocorticoid receptor, Nuclear receptor corepressor 1, 11-(4-DIMETHYLAMINO-PHENYL)-17-HYDROXY-13-METHYL-17-PROP-1-YNYL-1,2,6,7,8,11,12,13,14,15,16,17-DODEC AHYDRO-CYCLOPENTA[A]PHENANTHREN-3-ONE, ... (5 entities in total) |
| Functional Keywords | protein-ligand complex, nuclear receptor, peptide complex, hormone receptor 3, hormone receptor |
| Biological source | Homo sapiens (Human) More |
| Cellular location | Cytoplasm. Isoform Beta: Nucleus: P04150 Nucleus (By similarity): O75376 |
| Total number of polymer chains | 6 |
| Total formula weight | 123175.56 |
| Authors | Schoch, G.A.,Benz, J.,D'Arcy, B.,Stihle, M.,Burger, D.,Thoma, R.,Ruf, A. (deposition date: 2009-04-21, release date: 2009-12-01, Last modification date: 2023-11-01) |
| Primary citation | Schoch, G.A.,D'Arcy, B.,Stihle, M.,Burger, D.,Bar, D.,Benz, J.,Thoma, R.,Ruf, A. Molecular switch in the glucocorticoid receptor: active and passive antagonist conformations J.Mol.Biol., 395:568-577, 2010 Cited by PubMed Abstract: Mifepristone is known to induce mixed passive antagonist, active antagonist, and agonist effects via the glucocorticoid receptor (GR) pathway. Part of the antagonist effects of mifepristone are due to the repression of gene transcription mediated by the nuclear receptor corepressor (NCoR). Here, we report the crystal structure of a ternary complex of the GR ligand binding domain (GR-LBD) with mifepristone and a receptor-interacting motif of NCoR. The structures of three different conformations of the GR-LBD mifepristone complex show in the oxosteroid hormone receptor family how helix 12 modulates LBD corepressor and coactivator binding. Differences in NCoR binding and in helix 12 conformation reveal how the 11beta substituent in mifepristone triggers the helix 12 molecular switch to reshape the coactivator site into the corepressor site. Two observed conformations exemplify the active antagonist state of GR with NCoR bound. In another conformation, helix 12 completely blocks the coregulator binding site and explains the passive antagonistic effect of mifepristone on GR. PubMed: 19913032DOI: 10.1016/j.jmb.2009.11.011 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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