Structural insights into the mechanism of amine oxidation by monoamine oxidases A and B

• Published in: Archives of biochemistry and biophysics Vol. 464; no. 2; pp. 269 - 276
• Main Authors: Edmondson, Dale E., Binda, Claudia, Mattevi, Andrea
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.08.2007
• Subjects: Amine neurotransmitter; Amines - chemistry; Binding Sites; Catalysis; Computer Simulation; Enzyme Activation; Expression in Pichia pastoris; Flavin coenzymes; MAO A; MAO B; Models, Chemical; Models, Molecular; Monoamine Oxidase - chemistry; Monoamine oxidases; Oxidation-Reduction; Protein Binding; Protein Conformation; Proton abstraction; QSAR; Structure-Activity Relationship; X-ray structures; Flavin coenzymes; Amine neurotransmitter; QSAR; MAO B; MAO A; Expression in Pichia pastoris; Monoamine oxidases; X-ray structures; Proton abstraction
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2007.05.006

Due to their pharmacological importance in the oxidation of amine neurotransmitters, the membrane-bound flavoenzymes monoamine oxidase A and monoamine oxidase B have attracted numerous investigations and, as a result, two different mechanisms; the single electron transfer and the polar nucleophilic mechanisms, have been proposed to describe their catalytic mechanisms. This review compiles the recently available structural data on both enzymes with available mechanistic data as well as current NMR data on flavin systems to provide an integration of the approaches. These conclusions support the proposal that a polar nucleophilic mechanism for amine oxidation is the most consistent mechanistic scheme as compared with the single electron transfer mechanism.