A molecular model for the enzyme cytochrome P45017α, a major target for the chemotherapy of prostatic cancer

The enzyme cytochrome P45017α catalyses two key steps in the biosynthesis of the androgens from pregnanes: the 17α hydroxylation step and the subsequent 17–20 lyase reaction. Using a variety of techniques, including sequence alignment, secondary structure prediction, molecular mechanics and molecular dynamics, we have constructed a model for the three-dimensional structure of P45017α based on that of P450cam, the only cytochrome P450 enzyme for which the crystal structure is known. The model suggests the possibility of two modes of binding of steroid substrates at the active site, perhaps reflecting the dual functionality of the enzyme.