Molecular modelling of steroidogenic cytochromes P450 from families CYP11, CYP17, CYP19 and CYP21 based on the CYP102 crystal structure.

ABSTRACT

The results of homology modelling of mammalian steroidogenic cytochromes P450 (CYP) from families CYP11, CYP17, CYP19 and CYP21 are reported, based on a novel protein sequence alignment with CYP102, a bacterial P450 of known crystal structure. The molecular models generated from the CYP102 crystal structure template are consistent with experimental information from site-directed mutagenesis studies, steroidal substrate specificity and active site inhibitor studies. Interactive docking studies with both substrates and inhibitors of these enzymes indicate key residue interactions with the putative active site regions of each isoform investigated, which point to potential determinants of substrate specificity within these related enzymes.