Abstract
The human steroidogenic cytochrome P450 CYP17A1 catalyzes two types of reactions in the biosynthetic pathway leading from pregnenolone to testosterone and several other steroid hormones. The first is the hydroxylation of pregnenolone or progesterone to the corresponding 17α-hydroxy steroid, followed by a lyase reaction that converts these 17α-hydroxy intermediates to the androgens dehydroepiandrosterone and androstenedione, respectively. cytochrome
b
5
(cyt
b
5
) is known to act as both an effector and electron donor for the lyase oxidations, markedly stimulating the rate of the lyase reaction in its presence relative to the rate in its absence. Extensive sequential backbone
1
H,
15
N and
13
C nuclear magnetic resonance assignments have now been made for oxidized CYP17A1 bound to the prostate cancer drug and inhibitor abiraterone. This is the first eukaryotic P450 for which such assignments are now available. These assignments allow more complete interpretation of the structural perturbations observed upon cyt
b
5
addition. Possible mechanism(s) for the effector activity of cyt
b
5
are discussed in light of this new information.
Extensive sequential NMR resonance assignments in the human steroidogenic cytochrome P450 CYP17A1 permit detailed analysis of the interaction of cytochrome
b
5
with CYP17A1 that stimulates the ultimate production of testosterone and estrogen.