Resonance Raman spectroscopy of the oxygenated intermediates of human CYP19A1 implicates a compound i intermediate in the final lyase step.

Resonance Raman spectroscopy of the oxygenated intermediates of human CYP19A1 implicates a compound i intermediate in the final lyase step.
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DOI:
10.1021/ja500054c
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发表时间:
2014-04-02
影响因子:
15
通讯作者:
Kincaid JR
Kincaid JR
中科院分区:
化学1区
文献类型:
--
作者:
Mak PJ;Luthra A;Sligar SG;Kincaid JR

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CYP19A1(或芳香酶)是一种负责人类雌激素生物合成的细胞色素 P450,是治疗乳腺癌的重要治疗靶点。关于该关键酶中催化碳-碳断裂的反应中间体的身份仍然存在争议。使用共振拉曼光谱探测 CYP19A1 准备进行羟化酶和裂解酶化学反应的氧复合物,并与 CYP17A1 进行比较,我们发现 CYP19A1 中这两个步骤的频率或同位素位移没有显着差异。我们的实验表明化合物 I 参与 CYP19A1 催化的末端裂合酶步骤。
CYP19A1, or aromatase, a cytochrome P450 responsible for estrogen biosynthesis in humans, is an important therapeutic target for the treatment of breast cancer. There is still controversy surrounding the identity of reaction intermediate that catalyzes carbon–carbon scission in this key enzyme. Probing the oxy-complexes of CYP19A1 poised for hydroxylase and lyase chemistries using resonance Raman spectroscopy and drawing a comparison with CYP17A1, we have found no significant difference in the frequencies or isotopic shifts for these two steps in CYP19A1. Our experiments implicate the involvement of Compound I in the terminal lyase step of CYP19A1 catalysis.
DOI: 10.1126/science.1193478
发表时间: 2010-11-12
期刊: SCIENCE
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