Molecular modelling of CYP2B6, the human CYP2B isoform, by homology with the substrate-bound CYP102 crystal structure: evaluation of CYP2B6 substratecharacteristics, the cytochrome b(5) binding site and comparisons with CYP2B1 and CYP2B4

1. Molecular modelling studies of CYP2B isoforms from rat (CYP2B1), rabbit (CYP2B4) and man (CYP2B6) are reported, with particular emphasis on substra te interactions with the human CYP2B isoform, CYP2B6. 2. The findings represent an advance on our previous study that focused pri marily on the rat CYP2B isoform, CYP2B1, and involved homology modelling wi th substrate-free CYP102. 3. The current work utilizes the recently published substrate-bound CYP102 crystal structure as a template for construction of the CYP2B subfamily iso forms and shows, in particular, that known CYP2B6 substrate specificity and regioselectivity can be rationalized by putative active site interactions.