Structure of cytochrome P450eryF: Substrate, inhibitors, and model compounds bound in the active site

摘要

Much of our understanding of P450 reaction mechanisms derives from studies on P450cam, a bacterial camphor hydroxylase. P450cam has served as the model for understanding detailed structure/function relationships in mammalian P450 enzymes, which have not proved amenable to x-ray crystallographic techniques. To expand and improve the P450 model, we solved the structure of P450eryF, a cytochrome P450 involved in erythromycin biosynthesis. The overall structure of P45OeryF is similar to that of P45Ocam, but differs in the exact positioning of several a-helices, which results in the enlargement of the substrate-binding pocket.