Conformational dynamics in cytochrome P450-substrate interactions.

There now are four known cytochrome P450 crystal structures. Two of these, P450cam and P450eryF, are substrate-bound while P450terp and the heme domain of P450BM-3 are substrate-free. Here we describe a preliminary analysis of the P450BM-3 heme domain complexed with the 16-carbon fatty acid substrate, palmitoleic acid. A comparison of the substrate-free and -bound structures shows that a large conformational change in the substrate access channel accompanies substrate binding. This new information, together with the substrate-bound structures of P450cam and P450eryF, reveals which regions of P450 are the most important in controlling the dynamics of substrate binding and recognition.