Theoretical studies of cytochrome P-450. Characterization of stable and transient active states, reaction mechanisms and substrate-enzyme interactions.
The techniques of theoretical chemistry embodied in ab initio and semiempirical quantum mechanical and empirical energy methods have been used to elucidate the relationship between structure, spectra and function of the oxidative metabolizing heme proteins, the cytochrome P-450s, using a recent X-ray structure of a P-450cam-camphor complex. Specifically, the origin of the spin state changes when substrate binds to the oxidized resting state and the nature of the transient biologically active oxygen transfer state have been described. Mechanisms of hydroxylation and epoxidation, the two fundamental oxidative reactions performed by these enzymes, have been deduced and the role of substrate binding and orientation on product distribution investigated.
D001665:Binding Sites; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007700:Kinetics; D008722:Methods; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D012984:Software
D003577:Cytochrome P-450 Enzyme System