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

Balázs Krámos, Julianna Oláh

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11 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)279-300
Number of pages22
JournalStructural Chemistry
Issue number1
Publication statusPublished - Feb 2015



  • Androstenedione
  • C-C bond fission
  • Deformylation
  • QM/MM
  • Reaction mechanism

ASJC Scopus subject areas

  • Condensed Matter Physics
  • Physical and Theoretical Chemistry

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