The mechanism of human aromatase (CYP 19A1) revisited: DFT and QM/MM calculations support a compound I-mediated pathway for the aromatization process

Autor:	Julianna Oláh, Balázs Krámos
Rok vydání:	2014
Předmět:	chemistry.chemical_classification Reaction mechanism biology Stereochemistry Aromatization Electronic structure Condensed Matter Physics Ring (chemistry) QM/MM Enzyme chemistry biology.protein Physical and Theoretical Chemistry Aromatase Estrogen biosynthesis
Zdroj:	Structural Chemistry. 26:279-300
ISSN:	1572-9001 1040-0400
DOI:	10.1007/s11224-014-0545-9
Popis:	Human aromatase is responsible for the last step of estrogen biosynthesis, for the aromatization of ring A of androstenedione or testosterone. In this work, the mechanism of aromatization was studied using gas phase and hybrid QM/MM calculations. It is shown that human aromatase can efficiently catalyze the aromatization process via a compound I (or compound II)-mediated pathway. The nature of the oxidant is very sensitive to the polarizing environment of the enzyme, as the oxidant has a compound I nature in the gas phase calculations, which is modulated by the enzyme environment to become a mixed compound I and compound II character. The electronic structure of the obtained QM-only and QM/MM stationary points is thoroughly discussed.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::458476673aae7a8ba768d3bde3ba63e9 https://doi.org/10.1007/s11224-014-0545-9 Zobrazit plný text záznamu Full text from SpringerLink