The critical iron-oxygen intermediate in human aromatase

Stephanie L. Gantt, Ilia G. Denisov, Yelena V. Grinkova, Stephen G. Sligar

Research output: Contribution to journalArticlepeer-review


Aromatase (CYP19) is the target of several therapeutics used for breast cancer treatment and catalyzes the three-step conversion of androgens to estrogens, with an unusual C-C cleavage reaction in the third step. To better understand the CYP19 reaction, the oxy-ferrous complex of CYP19 with androstenedione substrate was cryotrapped, characterized by UV-vis spectroscopy, and cryoreduced to generate the next reaction cycle intermediate. EPR analysis revealed that the initial intermediate observed following cryoreduction is the unprotonated g1 = 2.254 peroxo-ferric intermediate, which is stable up to 180 K. Upon gradual cryoannealing, the low-spin (g1 = 2.39) product complex is formed, with no evidence for accumulation of the g1 = 2.30 hydroperoxo-ferric intermediate. The relative stabilization of the peroxo-ferric heme and the lack of observed hydroperoxo-ferric heme distinguish CYP19 from other P450s, suggesting that the proton delivery pathway is more hindered in CYP19 than in most other P450s.

Original languageEnglish (US)
Pages (from-to)169-173
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - Sep 11 2009


  • Aromatase
  • Cytochrome P450
  • EPR (electronic paramagnetic resonance)
  • Oxy-ferrous heme complex
  • Peroxo-ferric intermediate
  • Steroid biosynthesis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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