Resonance Raman Spectroscopy of the Oxygenated Intermediates of Human CYP19A1 Implicates a Compound I Intermediate in the Final Lyase Step
| Autor: | James R. Kincaid, Abhinav Luthra, Piotr J. Mak, Stephen G. Sligar |
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| Rok vydání: | 2014 |
| Předmět: |
endocrine system
Stereochemistry Resonance Raman spectroscopy Lyases Reaction intermediate Spectrum Analysis Raman 010402 general chemistry 01 natural sciences Biochemistry Catalysis 03 medical and health sciences Aromatase Colloid and Surface Chemistry Humans Bond cleavage 030304 developmental biology chemistry.chemical_classification 0303 health sciences biology Communication Androstenedione Cytochrome P450 General Chemistry Lyase 3. Good health 0104 chemical sciences Oxygen Enzyme chemistry CYP17A1 biology.protein Oxidation-Reduction |
| Zdroj: | Journal of the American Chemical Society |
| ISSN: | 1520-5126 0002-7863 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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