Recent advances in P450 research

P450 enzymes comprise a superfamily of heme-containing proteins that catalyze oxidative metabolism of structurally diverse chemicals. Over the past few years, there has been significant progress in P450 research on many fronts and the information gained is currently being applied to both drug development and clinical practice. Recently, a major accomplishment occurred when the structure of a mammalian P450 was determined by crystallography. Results from these studies will have a major impact on understanding structure-activity relationships of P450 enzymes and promote prediction of drug interactions. In addition, new technologies have facilitated the identification of several new P450 alleles. This information will profoundly affect our understanding of the causes attributed to interindividual variations in drug responses and link these differences to efficacy or toxicity of many therapeutic agents. Finally, the recent accomplishments towards constructing P450 null animals have afforded determination of the role of these enzymes in toxicity. Moreover, advances have been made towards the construction of humanized transgenic animals and plants. Overall, the outcome of recent developments in the P450 arena will be safer and more efficient drug therapies.