title: The use of the novel substrate-heme complex approach in the derivation of a representation of the active site of the enzyme complex 17alpha-hydroxylase and 17,20-lyase.
abstract: A novel molecular modelling technique, namely the substrate-heme complex (SHC) approach, is used to derive a representation of the overall active site of the enzyme complex 17alpha-hydroxylase (17alpha-OHase) and 17,20-lyase (lyase), a cytochrome P-450 dependent enzyme involved in the oxidative hydroxylation of the C(17) and cleavage of the C(17)-C(20) bond of the progestins (e.g., progesterone or pregnenolone). Using the derived model, we have rationalised the inhibitory activity of a number of steroidal and non-steroidal inhibitors, including miconazole and ketoconazole (the latter being a former potential treatment of hormone-dependent prostate cancer).
authors.affiliation: Department of Pharmacy, School of Chemical and Pharmaceutical Sciences, Kingston University, Penrhyn Road, Kingston upon Thames, Surrey, KT1 2EE, UK. S.AHMED@KINGSTON.AC.UK
authors.forename: Sabbir
authors.initials: S
authors.lastname: Ahmed
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001665:Binding Sites; D001671:Biochemistry / Q000379:methods*; D006418:Heme / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry; D006860:Hydrogen Bonding; D007654:Ketoconazole / Q000494:pharmacology; D008825:Miconazole / Q000494:pharmacology; D008956:Models, Chemical; D008958:Models, Molecular; D010100:Oxygen / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000737:chemistry*; D013256:Steroids / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D013256:Steroids; D006418:Heme; D008825:Miconazole; D006859:Hydrogen; D013254:Steroid 17-alpha-Hydroxylase; D007654:Ketoconazole; D010100:Oxygen