Protein-protein interactions in humans and porcine P450aromatase (CYP19) — ASN Events
  1. Schedule
  2. Session 5: Poster Session A
  3. Protein-protein interactions in humans and porcine P450aromatase (CYP19)

Protein-protein interactions in humans and porcine P450aromatase (CYP19) (#123)

Daphne Y.S. Wong 1 2 , Slavica Praporski 1 , Cynthia J. Corbin 3 , Alan J. Conley 3 , Dario Mizrachi 4 , Lisandra L. Martin 1 , Raymond J. Rodgers 2
  1. School of Chemistry, Monash University, Clayton, VIC, Australia
  2. Discipline of Obstetrics and Gynaecology, The University of Adelaide, Adelaide, SA, Australia
  3. School of Veterinary Medicine, University of California, Davis, CA, USA
  4. Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, USA

Aromatase is an important enzyme involved in the final step of oestrogen biosynthesis from androgens. Humans and other mammals encode one P450aromatase (P450arom/ CYP19) gene, however, the pig is the only exception, having three P450arom genes known as the porcine gonadal, placental and blastocyst isozymes (Conley et al., 1996; Corbin et al., 1995). The porcine gonadal P450arom has been reported to have very low oestrogen activity but higher substrate affinity compared to the human P450arom (Corbin et al., 2003). These differences could be due to their interactions with the substrate and/or some structural differences. Our Quartz Crystal Microbalance (QCM) data have shown differences in the binding of proteins to lipid membranes, for the human and porcine gonadal P450arom and with the redox-partner NADPH-cytochrome P450 oxidoreductase (CPR).  The results from Förster Resonance Energy Transfer (FRET) experiments with the human P450arom isozyme indicated homodimerisation of the human P450arom (Praporski et al., 2009). Together with the differences observed in the QCM results between the human and porcine gonadal P450arom we propose that the human P450arom functions as a homodimer, however, the porcine gonadal P450arom is consistent with a monomer; correlating well with its low catalytic activity. This study explores the underlying structural basis of the QCM and FRET data and employs molecular dynamics calculations together with these biophysical studies to investigate the protein-protein interactions. The structural and mechanistic differences between human and porcine aromatase could provide new insight to control oestrogen production.  

  1. Conley, A.J., Corbin, C.J., Hinshelwood, M.M., Liu, Z., Simpson, E.R., Ford, J.J., Harada, N. (1996) Functional aromatase expression in porcine adrenal gland and testis. Biology of Reproduction, 54, 497–505.
  2. Corbin, C.J., Mapes, S.M., Lee, Y.M., and Conley, A.J. (2003) Structural and functional differences among purified recombinant mammalian aromatases: glycosylation, N-terminal sequence and kinetic analysis of human, bovine and the porcine placental and gonadal isozymes. Molecular and Cellular Endocrinology. 206, 147-157.
  3. Corbin, C.J., Khalil, M.W., and Conley, A.J. (1995) Functional ovarian and placental isoforms of porcine aromatase. Molecular and Cellular Endocrinology, 113, 29-37.
  4. Praporski, S., Ng, S.M., Nguyen, A.D., Corbin, C.J., Mechler, A., Zheng, J., Conley, A.J., Martin, L.L. (2009) Organization of cytochrome P450 enzymes involved in sex steroid synthesis. The Journal of Biological Chemistry, 2B4, 33224-33232.