2. Academic Validation
  3. Steroidogenic cytochrome P450 17A1 structure and function

Steroidogenic cytochrome P450 17A1 structure and function

  • Mol Cell Endocrinol. 2021 May 15:528:111261. doi: 10.1016/j.mce.2021.111261.
Sarah D Burris-Hiday 1,  Emily E Scott 2
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI, USA. Electronic address: [email protected].
  • 2 Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI, USA; Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
PMID: 33781841 DOI: 10.1016/j.mce.2021.111261
Abstract

Cytochrome P450 17A1 (CYP17A1) is a critical steroidogenic enzyme, essential for producing glucocorticoids and sex Hormones. This review discusses the complex activity of CYP17A1, looking at its role in both the classical and backdoor steroidogenic pathways and the complex chemistry it carries out to perform both a hydroxylation reaction and a carbon-carbon cleavage, or lyase reaction. Functional and structural investigations have informed our knowledge of these two reactions. This review focuses on a few specific aspects of this discussion: the identities of reaction intermediates, the coordination of hydroxylation and lyase reactions, the effects of cytochrome b5, and conformational selection. These discussions improve understanding of CYP17A1 in a physiological setting, where CYP17A1 is implicated in a variety of steroidogenic diseases. This information can be used to improve ways in which CYP17A1 can be effectively modulated to treat diseases such as prostate and breast Cancer, Cushing's syndrome, and glioblastoma.

Keywords

Cancer; Crystallography; Cushing's syndrome; Cytochrome P450 17A1; Mechanism; Prostate.

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