Journal article
Evolutionary comparisons predict that dimerization of human cytochrome P450 aromatase increases its enzymatic activity and efficiency
LL Martin, JK Holien, D Mizrachi, CJ Corbin, AJ Conley, MW Parker, RJ Rodgers
Journal of Steroid Biochemistry and Molecular Biology | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2015
Abstract
Estrogen is an essential vertebrate hormone synthesized from androgens involving multiple hydroxylations, catalyzed by cytochrome P450 aromatase (P450arom or CYP19) enzymes. Despite their importance, very few comparative studies have been conducted on vertebrate and/or mammalian P450arom enzymes, either structurally or functionally. Here we directly compared the human (h-) and porcine gonadal (pg-) P450arom, as pg-P450arom has very low catalytic efficiency, with a ten-fold higher affinity (Km) for a substrate (androstenedione) and ten-fold reduction in turnover (Vmax). We recombinantly expressed these proteins and compared their interactions on a membrane using a quartz crystal microbalance ..
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Funding Acknowledgements
This research was supported by the National Health and Medical Research Council of Australia (NHMRC) and the Australian Research Council. We thank Dr. Slavica Praporski, Miss Daphne Y.S. Wong and Dr. Katja Hummitzsch for their assistance and Assoc. Professor Ashley Buckle for discussions on the molecular dynamics and Dr. Alexandr Simonov for thoughtful contributions. This work was also supported by a capital grant from the Australian Cancer Research Foundation and infrastructure funding from the Victorian Government (Australia) Operational Infrastructure Support Scheme to St. Vincent's Institute of Medical Research. M.W.P. is an NHMRC Research Fellow and J.K.H. is a joint Cure Cancer/Leukaemia Foundation Post-Doctoral Fellow.