Resonance Raman Spectroscopy of the Oxygenated Intermediates of Human CYP19A1 Implicates a Compound I Intermediate in the Final Lyase Step

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• 作者：Piotr J. Mak ; Abhinav Luthra ; Stephen G. Sligar ; James R. Kincaid
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：April 2, 2014
• 年：2014
• 卷：136
• 期：13
• 页码：4825-4828
• 全文大小：254K
• 年卷期：v.136,no.13(April 2, 2014)
• ISSN：1520-5126

文摘

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鈥揷arbon 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.