细胞色素P450 17A1（P450c17，CYP17A1）的多样化学性质。
The diverse chemistry of cytochrome P450 17A1 (P450c17, CYP17A1).
作者信息
Yoshimoto Francis K, Auchus Richard J
机构信息
Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, United States.
Division of Metabolism, Diabetes, and Endocrinology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48019, United States.
出版信息
J Steroid Biochem Mol Biol. 2015 Jul;151:52-65. doi: 10.1016/j.jsbmb.2014.11.026. Epub 2014 Dec 4.
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'.
摘要
细胞色素P450 17A1（CYP17A1）的类固醇羟基化和碳-碳键裂解活性分别负责糖皮质激素和雄激素的生成。抑制雄激素合成是治疗雄激素依赖性前列腺癌的重要策略。我们讨论了CYP17A1对各种底物的不同酶活性，证明了其底物选择性不高的特点。此外，还提出了F-G环与B'-螺旋之间一种新的螺旋间相互作用，以解释人CYP17A1以孕酮为底物时的16α-羟化酶活性。本文还总结了生物化学家研究这种重要酶所使用的技术。本文是名为“类固醇/甾醇信号传导”的特刊的一部分。
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