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

[Image: see text] 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 thi...

Descripción completa

Detalles Bibliográficos
Autores principales: Mak, Piotr J., Luthra, Abhinav, Sligar, Stephen G., Kincaid, James R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985783/
https://www.ncbi.nlm.nih.gov/pubmed/24645879
http://dx.doi.org/10.1021/ja500054c
_version_ 1782311626984128512
author Mak, Piotr J.
Luthra, Abhinav
Sligar, Stephen G.
Kincaid, James R.
author_facet Mak, Piotr J.
Luthra, Abhinav
Sligar, Stephen G.
Kincaid, James R.
author_sort Mak, Piotr J.
collection PubMed
description [Image: see text] 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.
format Online
Article
Text
id pubmed-3985783
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-39857832015-03-19 Resonance Raman Spectroscopy of the Oxygenated Intermediates of Human CYP19A1 Implicates a Compound I Intermediate in the Final Lyase Step Mak, Piotr J. Luthra, Abhinav Sligar, Stephen G. Kincaid, James R. J Am Chem Soc [Image: see text] 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. American Chemical Society 2014-03-19 2014-04-02 /pmc/articles/PMC3985783/ /pubmed/24645879 http://dx.doi.org/10.1021/ja500054c Text en Copyright © 2014 American Chemical Society
spellingShingle Mak, Piotr J.
Luthra, Abhinav
Sligar, Stephen G.
Kincaid, James R.
Resonance Raman Spectroscopy of the Oxygenated Intermediates of Human CYP19A1 Implicates a Compound I Intermediate in the Final Lyase Step
title Resonance Raman Spectroscopy of the Oxygenated Intermediates of Human CYP19A1 Implicates a Compound I Intermediate in the Final Lyase Step
title_full Resonance Raman Spectroscopy of the Oxygenated Intermediates of Human CYP19A1 Implicates a Compound I Intermediate in the Final Lyase Step
title_fullStr Resonance Raman Spectroscopy of the Oxygenated Intermediates of Human CYP19A1 Implicates a Compound I Intermediate in the Final Lyase Step
title_full_unstemmed Resonance Raman Spectroscopy of the Oxygenated Intermediates of Human CYP19A1 Implicates a Compound I Intermediate in the Final Lyase Step
title_short Resonance Raman Spectroscopy of the Oxygenated Intermediates of Human CYP19A1 Implicates a Compound I Intermediate in the Final Lyase Step
title_sort resonance raman spectroscopy of the oxygenated intermediates of human cyp19a1 implicates a compound i intermediate in the final lyase step
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985783/
https://www.ncbi.nlm.nih.gov/pubmed/24645879
http://dx.doi.org/10.1021/ja500054c
work_keys_str_mv AT makpiotrj resonanceramanspectroscopyoftheoxygenatedintermediatesofhumancyp19a1implicatesacompoundiintermediateinthefinallyasestep
AT luthraabhinav resonanceramanspectroscopyoftheoxygenatedintermediatesofhumancyp19a1implicatesacompoundiintermediateinthefinallyasestep
AT sligarstepheng resonanceramanspectroscopyoftheoxygenatedintermediatesofhumancyp19a1implicatesacompoundiintermediateinthefinallyasestep
AT kincaidjamesr resonanceramanspectroscopyoftheoxygenatedintermediatesofhumancyp19a1implicatesacompoundiintermediateinthefinallyasestep

Ejemplares similares