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• W2083670053 abstract "The glucocorticoid receptor (GR) is involved in the transcriptional regulation of genes associated with inflammation, glucose homeostasis, and bone turnover through the association with ligands, such as corticosteroids. GR-mediated gene transcription is regulated or fine-tuned via the recruitment of co-factors including coactivators and corepressors. Current therapeutic approaches to targeting GR aim to retain the beneficial anti-inflammatory activity of the corticosteroids while eliminating negative side effects. Towards achieving this goal the experiments discussed here reveal a mechanism of co-factor binding in the presence of either bound agonist or antagonist. The GR ligand binding domain (GR-LBD(F602S)), in the presence of agonist or antagonist, utilizes different modes of binding for coactivator versus corepressor. Coactivator binding to the co-effector binding pocket of GR-LBD(F602S) is driven both by favorable enthalpic and entropic interactions whereas corepressor binding to the same pocket is entropically driven. These data support the hypothesis that ligand-induced conformational changes dictate co-factor binding and subsequent trans-activation or trans-repression." @default.
• W2083670053 created "2016-06-24" @default.
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• W2083670053 date "2007-07-01" @default.
• W2083670053 modified "2023-09-25" @default.
• W2083670053 title "Agonist versus antagonist induce distinct thermodynamic modes of co-factor binding to the glucocorticoid receptor" @default.
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• W2083670053 doi "https://doi.org/10.1016/j.bpc.2007.03.013" @default.
• W2083670053 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17466438" @default.
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