Homology modelling of the enzyme P450 17 alpha-hydroxylase/17,20-lyase--a target for prostate cancer chemotherapy--from the crystal structure of P450BM-3.

Using homology modelling techniques the structure of cytochrome P450 17 alpha-hydroxylase/17-20 lyase (P450c17) has been predicted from the crystal structure of P450BM-3. The resulting structure has been compared to a previous model, built on the basis of homology to P450cam. Despite considerable structural differences between the two template structures, the two derived models for P450c17 show a high degree of similarity in the active-site region. As before, a bilobal active-site cavity is predicted, and we hypothesize that binding of the steroid in one lobe of the active site is associated with the hydroxylase activity of the enzyme, whilst binding in the other is associated with the lyase reaction.