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2
Resonance Raman spectroscopy of the oxygenated intermediates of human CYP19A1 implicates a compound i intermediate in the final lyase step.人细胞色素P450 19A1（CYP19A1）氧化中间体的共振拉曼光谱表明，在最终裂解步骤中存在一种化合物I中间体。
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Aromatase reaction of 3-deoxyandrogens: steric mode of the C-19 oxygenation and cleavage of the C10-C19 bond by human placental aromatase.3-脱氧雄激素的芳香化酶反应：人胎盘芳香化酶对C-19的氧化作用及C10-C19键断裂的空间模式
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Role of Water in the Puzzling Mechanism of the Final Aromatization Step Promoted by the Human Aromatase Enzyme. Insights from QM/MM MD Simulations.水在人芳香酶促进的最终芳构化步骤的神秘机制中的作用。QM/MM MD 模拟的见解。
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7
QM/MM modeling of the hydroxylation of the androstenedione substrate catalyzed by cytochrome P450 aromatase (CYP19A1).细胞色素P450芳香化酶（CYP19A1）催化雄烯二酮底物羟基化的量子力学/分子力学建模
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Evaluation of the mechanism of aromatase cytochrome P450. A site-directed mutagenesis study.芳香化酶细胞色素P450作用机制的评估。一项定点诱变研究。
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19-Hydroxylation of androgens by rat granulosa cells.大鼠颗粒细胞对雄激素的19-羟化作用。
Endocrinology. 1988 Mar;122(3):1047-52. doi: 10.1210/endo-122-3-1047.

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19-hydroxy Steroids in the Aromatase Reaction: Review on Expression and Potential Functions.芳香化酶反应中的19-羟基类固醇：表达及潜在功能综述
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本文引用的文献

1
Resonance Raman spectroscopy of the oxygenated intermediates of human CYP19A1 implicates a compound i intermediate in the final lyase step.人细胞色素P450 19A1（CYP19A1）氧化中间体的共振拉曼光谱表明，在最终裂解步骤中存在一种化合物I中间体。
J Am Chem Soc. 2014 Apr 2;136(13):4825-8. doi: 10.1021/ja500054c. Epub 2014 Mar 25.
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Active site proton delivery and the lyase activity of human CYP17A1.人 CYP17A1 的活性部位质子传递和裂合酶活性。
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Kinetic solvent isotope effect in human P450 CYP17A1-mediated androgen formation: evidence for a reactive peroxoanion intermediate.人细胞色素P450 CYP17A1介导雄激素生成中的动力学溶剂同位素效应：反应性过氧阴离子中间体的证据。
J Am Chem Soc. 2013 Nov 6;135(44):16245-7. doi: 10.1021/ja4086403. Epub 2013 Oct 29.
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Structural basis for the functional roles of critical residues in human cytochrome p450 aromatase.人细胞色素 P450 芳香酶关键残基功能作用的结构基础。
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Synergistic effects of mutations in cytochrome P450cam designed to mimic CYP101D1.设计模拟 CYP101D1 的细胞色素 P450cam 突变的协同效应。
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Nanodiscs in the studies of membrane-bound cytochrome P450 enzymes.用于膜结合细胞色素P450酶研究的纳米圆盘
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Nanodiscs as a new tool to examine lipid-protein interactions.纳米圆盘作为研究脂-蛋白相互作用的新工具。
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Cytochromes P450 in nanodiscs.纳米盘中的细胞色素P450
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Functional reconstitution of monomeric CYP3A4 with multiple cytochrome P450 reductase molecules in Nanodiscs.在纳米盘里用多个细胞色素 P450 还原酶分子对单体 CYP3A4 进行功能重建。
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10
Kinetic analysis of the three-step steroid aromatase reaction of human cytochrome P450 19A1.三步甾体芳香酶反应的动力学分析 ：人细胞色素 P45019A1 的作用。
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CYP19A1稳态周转中的动力学溶剂同位素效应表明化合物1参与了羟基化和芳构化步骤。

Kinetic solvent isotope effect in steady-state turnover by CYP19A1 suggests involvement of Compound 1 for both hydroxylation and aromatization steps.

作者信息

Khatri Yogan, Luthra Abhinav, Duggal Ruchia, Sligar Stephen G

机构信息

Department of Biochemistry, University of Illinois Urbana-Champaign, 505 S. Goodwin Avenue, Urbana, IL 61801, United States.

Department of Biochemistry, University of Illinois Urbana-Champaign, 505 S. Goodwin Avenue, Urbana, IL 61801, United States.

出版信息

FEBS Lett. 2014 Aug 25;588(17):3117-22. doi: 10.1016/j.febslet.2014.06.050. Epub 2014 Jul 2.

DOI:10.1016/j.febslet.2014.06.050
PMID:24997347
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4138292/
Abstract

CYP19A1, or human aromatase catalyzes the conversion of androgens to estrogens in a three-step reaction through the formation of 19-hydroxy and 19-aldehyde intermediates. While the first two steps of hydroxylation are thought to proceed through a high-valent iron-oxo species, controversy exists surrounding the identity of the reaction intermediate that catalyzes the lyase and aromatization reaction. We investigated the kinetic isotope effect on the steady-state turnover of Nanodisc-incorporated human CYP19A1 to explore the mechanisms of this reaction. Our experiments reveal a significant (∼ 2.5) kinetic solvent isotope effect for the C10-C19 lyase reaction, similar to that of the first two hydroxylation steps (2.7 and 1.2). These data implicate the involvement of Compound 1 as a reactive intermediate in the final aromatization step of CYP19A1.

摘要

CYP19A1，即人类芳香化酶，通过形成19-羟基和19-醛中间体，在三步反应中将雄激素转化为雌激素。虽然羟基化的前两步被认为是通过高价铁-氧物种进行的，但关于催化裂解酶和芳香化反应的反应中间体的身份存在争议。我们研究了对纳米盘包埋的人类CYP19A1稳态周转的动力学同位素效应，以探索该反应的机制。我们的实验揭示了C10-C19裂解酶反应存在显著的（约2.5）动力学溶剂同位素效应，这与前两个羟基化步骤（2.7和1.2）相似。这些数据表明化合物1作为反应中间体参与了CYP19A1的最终芳香化步骤。