期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 528, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2021.111261
关键词
Mechanism; Crystallography; Prostate; Cancer; Cushing' s syndrome
资金
- National Institutes of Health [R37 GM076343]
CYP17A1 is a critical enzyme involved in steroid synthesis, carrying out both hydroxylation and lyase reactions. This review discusses the complex activity of CYP17A1, focusing on reaction intermediates, coordination of reactions, the role of cytochrome b5, and conformational selection, which can improve our understanding of treating related diseases.
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.
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