title: The catalytic mechanism of protein phosphatase 5 established by DFT calculations.
abstract: In order to elucidate the catalytic mechanism of the Mn-Mn containing serine/threonine protein phosphatase 5 (PP5), we present a density functional theory study with a cluster model approach. According to our results, the reaction occurs through an in-line concerted transition state with an energy of 15.8 kcal mol(-1) , and no intermediates are formed. The important role played by His304 and Asp274 as stabilizers of the leaving group has been shown, whereas the role played by the metal ions seems to be mostly electrostatic. The indispensable requirement of having a neutral active center has been demonstrated by testing different protonation states of the cluster model. We have shown also the importance of describing properly the electronic configuration of the Mn-Mn binuclear centers.
authors.affiliation: Dipartimento di Chimica, Università della Calabria, 87036 Arcavacata di Rende (Italia); REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, s/n 4169-007 Porto (Portugal).
authors.forename: António J M
authors.initials: AJ
authors.lastname: Ribeiro
authors.forename: Marta E
authors.initials: ME
authors.lastname: Alberto
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Ramos
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Fernandes
authors.forename: Nino
authors.initials: N
authors.lastname: Russo
mesh_terms: D002384:Catalysis; D007477:Ions / Q000737:chemistry; D008345:Manganese / Q000737:chemistry*; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry*; D010749:Phosphoprotein Phosphatases / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: D007477:Ions; D009687:Nuclear Proteins; D008345:Manganese; D010749:Phosphoprotein Phosphatases; C089641:protein phosphatase 5
keywords: density functional calculations; enzyme catalysis; manganese; metalloenzymes; nucleophilic substitution