Abstract

Monoamine Oxidase B (MAO B) is a flavoenzyme that regulates and oxidizes monoamine neurotransmitters such as adrenaline, noradrenaline and dopamine. The oxidation reaction also produces hydrogen peroxide that can be harmful to dopaminergic neurons leading to neurological disorders such as Alzheimer’s disease and Parkinson’s disease. MAO B inhibitor is consequently used for preventing those neurological disorders. The structural details insight into the oxidation reaction mechanism of MAO B are vital to design specific inhibitors. A theoretical study is used to explain structural details of theoretical states in molecular level. In this work, the deamination reaction of adrenaline by MAO B was carried out to gain molecular-level details via ONIOM technique at M062X/6–31+G(d,p):PM6 level of theory. According to ONIOM calculation results, there are 4 key MAO B active site residues which are Leu171, Phe343, Tyr398 and Tyr435. Residues that bind adrenaline via hydrophobic interactions are Leu171, Phe343 and Tyr398 while Tyr435 binds via hydrogen bond. Additionally, NBO analysis suggests that the mechanism of this reaction is a hybrid between hydride transfer and polar nucleophilic characters.