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

Document Type

Article

Language

eng

Format of Original

4 p.

Publication Date

4-2-2014

Publisher

American Chemical Society

Source Publication

Journal of the American Chemical Society

Source ISSN

0002-7863

Original Item ID

DOI: 10.1021/ja500054c

Abstract

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.

Comments

Published version. Journal of the American Chemical Society, Vol. 136, No. 13 (April 2014): 4825-4828. DOI. © 2014 American Chemical Society. Used with permission.

ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

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