A Proposal for Mitochondrial Processing Peptidase Catalytic Mechanism

The reaction Mechanism of the Mitochondrial Processing Peptidase enzyme (MPP) was investigated by using hybrid density functional theory. This enzyme removes the NH2-terminal targeting signals of nuclear-encoded mitochondrial protein precursors in the mitochondrial matrix. The catalytic process was studied using a model for the active site consisting of 161 atoms locating all the stationary points on the potential energy curve and determining the main energetic, structural, and electronic features that drive the catalysis. Despite the differences between the B3LYP and MPWB1K descriptions, it is possible hypothesize that the step of the reaction is most likely the nucleophilic attack of zinc bound hydroxide to a carbonyl carbon of the substrate. The results allowed assignment of the proper roles to some active site residues in this mechanism.