title: A proposal for mitochondrial processing peptidase catalytic mechanism.
abstract: The reaction mechanism of the Mitochondrial Processing Peptidase enzyme (MPP) was investigated by using hybrid density functional theory. This enzyme removes the NH(2)-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 rate-limiting 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.
authors: Dipartimento di Chimica, Universita' della Calabria, I-87030 Arcavacata di Rende (CS), Italy.
authors: Orazio
authors: O
authors: Amata
authors: Tiziana
authors: T
authors: Marino
authors: Nino
authors: N
authors: Russo
authors: Marirosa
authors: M
authors: Toscano
mesh_terms: D055162:Biocatalysis; D008928:Mitochondria / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011789:Quantum Theory
chemical_list: D010447:Peptide Hydrolases