We investigated the 16?-hydroxylation of steroid molecules and regioselective binding mode in homology-modeled cytochrome\nP450-2C11 to correlate the biological study with the computational molecular modeling. It revealed that there was a positive\nrelationship between the observed inhibitory potencies and the binding free energies. Docking of steroid molecules into this\nhomology-modeled CYP2C11 indicated that 16?-hydroxylation is favored with steroidal molecules possessing the following\ncomponents, (1) a bent A-B ring configuration (5?-reduced), (2) C-3 ?-hydroxyl group, (3) C-17?-acetyl group, and (4) methyl\ngroup at both the C-18 and C-19. These respective steroid components requirements were defined as the inhibitory contribution\nfactor. Overall studies of the male rat CYP2C11 metabolism revealed that the above-mentioned steroid components requirements\nwere essential to induce an effective inhibition of [3H]progesterone 16?-hydroxylation. As far as docking of homology-modeled\nCYP2C11 against investigated steroids is concerned, they are docked at the active site superimposed with flurbiprofen. It was also\nfound that the distance between heme iron and C16?-H was between 4 to 6 ?A and that the related angle was in the range of\n180 �± 45?.
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