Determination of regions important for Monoamine oxidase (MAO) A and B substrate and inhibitor selectivities

MAO-A and -B are defined by their substrate and inhibitor preferences. To determine which regions of the isoenzymes confer these preferences, we have constructed six chimeric MAO enzymes by reciprocally exchanging corresponding N-terminal, C-terminal, and internal segments of MAO-A and -B then determined the catalytic properties of these chimeric enzymes. N-terminal chimerics A(45)B and B(36)A were made by exchanging amino acid segments 1-45 and 1-36 of MAO-A and -B respectively. C-terminal chimerics A(402)B and B(393)A were made by exchanging amino acid segments 403-527 and 394-520 of MAO-A and -B respectively, and internal chimerics AB(161-375)A and BA(152-366)B were made by exchanging amino acid segments 161-375 and 152-366 of MAO-A and -B respectively. The enzymatic properties observed for the chimerics suggest that the exchanged internal regions but not the N- or C-terminal regions confer substrate and inhibitor preferences.