title: Studies on 16α-Hydroxylation of Steroid Molecules and Regioselective Binding Mode in Homology-Modeled Cytochrome P450-2C11.
abstract: We investigated the 16α-hydroxylation of steroid molecules and regioselective binding mode in homology-modeled cytochrome P450-2C11 to correlate the biological study with the computational molecular modeling. It revealed that there was a positive relationship between the observed inhibitory potencies and the binding free energies. Docking of steroid molecules into this homology-modeled CYP2C11 indicated that 16α-hydroxylation is favored with steroidal molecules possessing the following components, (1) a bent A-B ring configuration (5β-reduced), (2) C-3 α-hydroxyl group, (3) C-17β-acetyl group, and (4) methyl group at both the C-18 and C-19. These respective steroid components requirements were defined as the inhibitory contribution factor. Overall studies of the male rat CYP2C11 metabolism revealed that the above-mentioned steroid components requirements were essential to induce an effective inhibition of [(3)H]progesterone 16α-hydroxylation. As far as docking of homology-modeled CYP2C11 against investigated steroids is concerned, they are docked at the active site superimposed with flurbiprofen. It was also found that the distance between heme iron and C16α-H was between 4 to 6 Å and that the related angle was in the range of 180 ± 45°.
authors: Faculty of Pharmacy, Helwan University, Ain Helwan, Cairo 11795, Egypt.
authors: Hamed I
authors: HI
authors: Ali
authors: Department of Chemistry, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors: Morio
authors: M
authors: Yamada
authors: Liberal Arts Center, Hyogo University of Health Sciences, 1-3-6, Minatojima, Chuo-ku, Kobe 650-8530, Japan.
authors: Yukihisa
authors: Y
authors: Fujita
authors: Faculty of Pharmaceutical Sciences, Center for Area Research and Development (CARD), Kobe Gakuin University, 1-1-3, Minatojima, Chuo-ku, Kobe 650-8586, Japan.
authors: Mitsuko
authors: M
authors: Maeda
authors: Faculty of Pharmaceutical Sciences, Center for Area Research and Development (CARD), Kobe Gakuin University, 1-1-3, Minatojima, Chuo-ku, Kobe 650-8586, Japan.
authors: Eiichi
authors: E
authors: Akaho