Influence of C Terminus on Monoamine Oxidase A and B Catalytic Activity

Abstract: Monoamine oxidase (MAO) A and B play important roles in the metabolism of neurotransmitters and dietary amines. The domains important for enzyme specificities were studied by construction of chimeric MAOA/B enzymes. Exchange of the N-terminal 45 amino acids of MAOA with the N-terminal 36 residues of MAOB (chimeric enzymes B₃₆A and A₄₅B) resulted in the same substrate and inhibitor sensitivities as the wild-type MAOA or B. Thus, the N terminus may not be responsible for MAOA or B enzyme specificities. When MAOB C-terminal residues 393–520 were replaced with MAOA C-terminal residues 402–527 (chimeric B₃₉₃A) catalytic activity was not detectable. Chimeric B₃₉₃A consists of eight residues with different charges, three less proline residues (458, 476, and 490), and one additional proline at 518 compared with wild-type MAOB. These differences may have induced conformational changes and affected MAOB catalytic activity. Thus, the C terminus of MAOB is critical for maintaining MAOB in an active form. It is interesting that when the C terminus of MAOA was switched with MAOB (chimeric A₄₀₂B), little effect was observed on MAOA catalytic activity. This new information is valuable for further studies of the structure and function relationship of this important enzyme.