title: 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.
authors.affiliation: Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles 90033, USA.
authors.forename: K
authors.initials: K
authors.lastname: Chen
authors.forename: H F
authors.initials: HF
authors.lastname: Wu
authors.forename: J C
authors.initials: JC
authors.lastname: Shih
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002384:Catalysis; D002460:Cell Line; D008969:Molecular Sequence Data; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D014162:Transfection
chemical_list: D011993:Recombinant Fusion Proteins; D008995:Monoamine Oxidase