Cytochrome P450 Structure, Mechanism, and Biochemistry

In the ten years that have elapsed since the first edition of this book went to press, the cytochrome P450 field has completed the transition to a discipline in which structure and mechanism, even regulation and biological function, are dealt with in molecular terms. The twin forces that have propelled this remarkable progress have been the widespread adoption of molecular biological approaches and the successful application of modem structural techniques. Only a few P450 primary sequences were available in 1985, whereas hundreds of P450 sequences are now available. Site-specific mutagenesis was then mostly a proverbial gleam in the eye of the P450 community, but it is now a standard technique in the research repertoire. The first crystal structure of a cytochrome P450 enzyme had just been solved in 1985 and appeared on the cover of the first edition. Today, the high-reso lution crystal structures of four soluble bacterial P450 enzymes are available and the race is on to develop approaches that will permit us to determine the structures of the membrane-bound forms of the enzyme. The past ten years has seen phenomenal progress let us hope that the next ten will prove equally exciting. The book is informally divided into four sections. In order to hold the book close to the advancing front of research, some of the chapter topics from the first edition have been dropped to make room for new or expanded topics.