title: Triesterase and promiscuous diesterase activities of a di-Co(II)-containing organophosphate degrading enzyme reaction mechanisms.
abstract: The reaction mechanism for the hydrolysis of trimethyl phosphate and of the obtained phosphodiester by the di-Co(II) derivative of organophosphate degrading enzyme from Agrobacterium radiobacter P230(OpdA), have been investigated at density functional level of theory in the framework of the cluster model approach. Both mechanisms proceed by a multistep sequence and each catalytic cycle begins with the nucleophilic attack by a metal-bound hydroxide on the phosphorus atom of the substrate, leading to the cleavage of the phosphate-ester bond. Four exchange-correlation functionals were used to derive the potential energy profiles in protein environments. Although the enzyme is confirmed to work better as triesterase, as revealed by the barrier heights in the rate-limiting steps of the catalytic processes, its promiscuous ability to hydrolyze also the product of the reaction has been confirmed. The important role played by water molecules and some residues in the outer coordination sphere has been elucidated, while the binuclear Co(II) center accomplishes both structural and catalytic functions. To correctly describe the electronic configuration of the d shell of the metal ions, high- and low-spin arrangement jointly with the occurrence of antiferromagnetic coupling, have been herein considered.
authors.affiliation: Dipartimento di Chimica e Tecnologie Chimiche and Centro di Calcolo ad Alte Prestazioni per Elaborazioni Parallele e Distribuite-Centro d'Eccellenza MIUR, Università della Calabria, 87036 Arcavacata di Rende (CS) (Italy).
authors.forename: Marta E
authors.initials: ME
authors.lastname: Alberto
authors.forename: Gaspar
authors.initials: G
authors.lastname: Pinto
authors.forename: Nino
authors.initials: N
authors.lastname: Russo
authors.forename: Marirosa
authors.initials: M
authors.lastname: Toscano
mesh_terms: D001665:Binding Sites; D055162:Biocatalysis; D003035:Cobalt / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004950:Esterases / Q000737:chemistry*; D059346:Magnets; D008958:Models, Molecular; D009943:Organophosphorus Compounds / Q000737:chemistry*; D013379:Substrate Specificity
chemical_list: D009943:Organophosphorus Compounds; D003035:Cobalt; D004950:Esterases
keywords: computational chemistry; density functional calculations; enzyme catalysis; reaction mechanisms