Mechanistic scrutiny identifies a kinetic role for cytochrome b5 regulation of human cytochrome P450c17 (CYP17A1, P450 17A1)

Alexandr N. Simonov, Jessica K. Holien, Joyee Chun In Yeung, Ann D. Nguyen, C. Jo Corbin, Jie Zheng, Vladimir L. Kuznetsov, Richard J. Auchus, Alan J Conley, Alan M. Bond, Michael W. Parker, Raymond J. Rodgers, Lisandra L. Martin

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Cytochrome P450c17 (P450 17A1, CYP17A1) is a critical enzyme in the synthesis of androgens and is now a target enzyme for the treatment of prostate cancer. Cytochrome P450c17 can exhibit either one or two physiological enzymatic activities differentially regulated by cytochrome b5. How this is achieved remains unknown. Here, comprehensive in silico, in vivo and in vitro analyses were undertaken. Fluorescence Resonance Energy Transfer analysis showed close interactions within living cells between cytochrome P450c17 and cytochrome b5. In silico modeling identified the sites of interaction and confirmed that E48 and E49 residues in cytochrome b5 are essential for activity. Quartz crystal microbalance studies identified specific protein-protein interactions in a lipid membrane. Voltammetric analysis revealed that the wild type cytochrome b5, but not a mutated, E48G/E49G cyt b5, altered the kinetics of electron transfer between the electrode and the P450c17. We conclude that cytochrome b5 can influence the electronic conductivity of cytochrome P450c17 via allosteric, protein-protein interactions.

Original languageEnglish (US)
Article numbere0141252
JournalPLoS One
Issue number11
StatePublished - Nov 1 2015

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)


Dive into the research topics of 'Mechanistic scrutiny identifies a kinetic role for cytochrome b5 regulation of human cytochrome P450c17 (CYP17A1, P450 17A1)'. Together they form a unique fingerprint.

Cite this