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_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. © 1999 Society of Chemical Industry