title: Revealing Monoamine Oxidase B Catalytic Mechanisms by Means of the Quantum Chemical Cluster Approach.
abstract: Two of the possible catalytic mechanisms for neurotransmitter oxidative deamination by monoamine oxidase B (MAO B), namely, polar nucleophilic and hydride transfer, were addressed in order to comprehend the nature of their rate-determining step. The Quantum Chemical Cluster Approach was used to obtain transition states of MAO B complexed with phenylethylamine (PEA), benzylamine (BA), and p-nitrobenzylamine (NBA). The choice of these amines relies on their importance to address MAO B catalytic mechanisms so as to help us to answer questions such as why BA is a better substrate than NBA or how para-substitution affects substrate's reactivity. Transition states were later validated by comparison with the experimental free energy barriers. From a theoretical point of view, and according to the our reported transition states, their calculated barriers and structural and orbital differences obtained by us among these compounds, we propose that good substrates such as BA and PEA might follow the hydride transfer pathway while poor substrates such as NBA prefer the polar nucleophilic mechanism, which might suggest that MAO B can act by both mechanisms. The low free energy barriers for BA and PEA reflect the preference that MAO B has for hydride transfer over the polar nucleophilic mechanism when catalyzing the oxidative deamination of neurotransmitters.
authors.affiliation: †Molecular Graphics Suite, Department of Inorganic and Analytical Chemistry, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile.
authors.forename: Gerald
authors.initials: G
authors.lastname: Zapata-Torres
authors.affiliation: ‡Facultad de Química, Departamento de Química Orgánica, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Angélica
authors.initials: A
authors.lastname: Fierro
authors.affiliation: §Universidad Andres Bello, Facultad de Ciencias Exactas, Departamento de Ciencias Quimicas, Avenida República 275, 8370146 Santiago, Chile.
authors.forename: German
authors.initials: G
authors.lastname: Barriga-González
authors.affiliation: ∥Laboratory of Process Modeling and Distributed Computing, Department of Chemical Engineering and Biotechnology, University of Chile, Beauchef 850, Santiago, Chile.
authors.forename: J Cristian
authors.initials: JC
authors.lastname: Salgado
authors.affiliation: §Universidad Andres Bello, Facultad de Ciencias Exactas, Departamento de Ciencias Quimicas, Avenida República 275, 8370146 Santiago, Chile.
authors.forename: Cristian
authors.initials: C
authors.lastname: Celis-Barros
mesh_terms: D020816:Amino Acid Motifs; D001596:Benzylamines / Q000378:metabolism; D055162:Biocatalysis; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism*; D010627:Phenethylamines / Q000378:metabolism; D011789:Quantum Theory; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D001596:Benzylamines; D010627:Phenethylamines; D014867:Water; C048768:4-nitrobenzylamine; C030796:benzylamine; D008995:Monoamine Oxidase