A ROLE FOR THR-252 IN CYTOCHROME-P450CAM OXYGEN ACTIVATION

Molecular dynamics simulations of the ferrous dioxygen bound form of wild type cytochrome P450cam were performed and the results analyzed to reveal the time-dependent interactions of T252 with surrounding residues as well as with the bound oxygen. The results indicate a time-dependent bimodal interaction of T252 with both G248 and the terminal oxygen of the bound dioxygen. The hydrogen bonding interaction of T252 with these two moieties is ''anticorrelated'' in the sense that the breaking of the T252-G248 hydrogen bond is concurrent with formation of the T252-dioxygen interaction. These simulations support the probability of a role of T252 in stabilization of the initial dioxygen bound complex and promotion of subsequent formation of compound I previously indicated by several experimental studies.