Structure-Based Recombination of Cytochrome P450

California Institute Of Technology, Pasadena CA

Investigators

Abstract

DESCRIPTION (provided by applicant): Cytochromes P450 are ubiquitous in nature and catalyze a wide range of reactions involved in detoxification of xenobiotics and metabolism of various physiologically important compounds. Despite acting upon a broad range of substrates, P450s are characterized by a similar spatial fold, which offers a unique opportunity to investigate the evolution of novel activities within a single structural framework. By constructing libraries of P450 chimeras, and screening them for recombination events that generate folded and functional enzymes, a better understanding of how evolution explores sequence, structural, and functional diversity will be achieved. Furthermore, these studies will lead to a better understanding of how proteins can be engineered to develop new biomaterials and protein-based therapeutics, especially for their use in prodrug therapies to treat cancer as well as for other biomedical process such their use in biodrug delivery systems.