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J Steroid Biochem Mol Biol. 2015 Jul;151:52-65. doi: 10.1016/j.jsbmb.2014.11.026. Epub 2014 Dec 4.

The diverse chemistry of cytochrome P450 17A1 (P450c17, CYP17A1).

Author information

1
Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, United States.
2
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.

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'.

KEYWORDS:

17,20-Lyase; 17-Hydroxylase; Androgen; Cytochrome P450; Hypertension; Metabolic switching; Steroidogenesis

PMID:
25482340
PMCID:
PMC4456341
DOI:
10.1016/j.jsbmb.2014.11.026
[Indexed for MEDLINE]
Free PMC Article

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