title: The diverse chemistry of cytochrome P450 17A1 (P450c17, CYP17A1).
abstract: The steroid hydroxylation and carbon-carbon bond cleavage activities of cytochrome P450 17A1 (CYP17A1) are responsible for the production of glucocorticoids and androgens, respectively. The inhibition of androgen synthesis is an important strategy to treat androgen-dependent prostate cancer. We discuss the different enzymatic activities towards the various substrates of CYP17A1, demonstrating its promiscuity. Additionally, a novel interhelical interaction is proposed between the F-G loop and the B'-helix to explain the 16α-hydroxylase activity of human CYP17A1 with progesterone as the substrate. The techniques used by biochemists to study this important enzyme are also summarized. This article is part of a Special Issue entitled 'Steroid/Sterol signaling'.
authors.affiliation: Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, United States.
authors.forename: Francis K
authors.initials: FK
authors.lastname: Yoshimoto
authors.affiliation: Division of Metabolism, Diabetes, and Endocrinology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48019, United States. Electronic address: rauchus@med.umich.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Auchus
mesh_terms: D000818:Animals; D002384:Catalysis; D006801:Humans; D013254:Steroid 17-alpha-Hydroxylase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013256:Steroids / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D013256:Steroids; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase
keywords: 17,20-Lyase; 17-Hydroxylase; Androgen; Cytochrome P450; Hypertension; Metabolic switching; Steroidogenesis