Piperonyl butoxide-mediated inhibition of cytochrome P450-catalysed insecticide metabolism: a rational approach

The inhibitory effect of piperonyl butoxide (PBO) on cytochrome P450 was studied by theoretical methods. Binding conformations of PBO were obtained by the recently developed low-mode conformational search within the active site of cytochrome P450 sub(cam). Increased activity of PBO relative to other methylendioxyphenyl inhibitors was rationalized by its decreased conformational mobility and the steric block created by its long side-chain in the substrate access channel of the enzyme.