Resonance Raman spectroscopy of the oxygenated intermediates of human CYP19A1 implicates a compound i intermediate in the final lyase step. J Am Chem Soc 2014 Apr 02;136(13):4825-8
Date
03/22/2014Pubmed ID
24645879Pubmed Central ID
PMC3985783DOI
10.1021/ja500054cScopus ID
2-s2.0-84897514620 (requires institutional sign-in at Scopus site) 46 CitationsAbstract
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.
Author List
Mak PJ, Luthra A, Sligar SG, Kincaid JRAuthor
James Kincaid PhD Department Chair and Professor, Biophysical Chemistry in the Chemistry department at Marquette UniversityMESH terms used to index this publication - Major topics in bold
AndrostenedioneAromatase
Humans
Lyases
Oxidation-Reduction
Oxygen
Spectrum Analysis, Raman