Lewis D F V, Ogg M S, Goldfarb P S, Gibson G G
School of Biomedical and Life Sciences, University of Surrey, Surrey GU2 7XH, Guildford, UK.
J Steroid Biochem Mol Biol. 2002 Oct;82(2-3):195-9. doi: 10.1016/s0960-0760(02)00158-9.
The results of homology modelling of the human glucorticoid receptor (hGR) ligand-binding domain (LBD) based on the ligand-bound domain of the human estrogen receptor alpha (hERalpha) are reported. It is shown that known hGR ligands which induce the human cytochrome P450 enzyme CYP3A4 are able to fit the putative ligand-binding site of the nuclear hormone receptor and form hydrogen bonds with key amino acid residues within the binding pocket. Quantitative structure-activity relationships (QSARs) have been derived for hGR-mediated CYP3A4 induction which involve certain molecular structural and physicochemical properties of the ligand themselves, yielding good correlations (R=0.96-0.98) with fold induction of CYP3A4 known to be mediated via hGR involvement.
报道了基于人雌激素受体α（hERα）配体结合域对人糖皮质激素受体（hGR）配体结合域（LBD）进行同源建模的结果。结果表明，已知能诱导人细胞色素P450酶CYP3A4的hGR配体能够契合核激素受体的假定配体结合位点，并与结合口袋内的关键氨基酸残基形成氢键。已得出hGR介导的CYP3A4诱导的定量构效关系（QSAR），其涉及配体自身的某些分子结构和物理化学性质，与已知通过hGR参与介导的CYP3A4诱导倍数具有良好的相关性（R = 0.96 - 0.98）。
