title: Determination of regions important for monoamine oxidase (MAO) A and B substrate and inhibitor selectivities.
abstract: 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 A45B and B36A were made by exchanging amino acid segments 1-45 and 1-36 of MAO-A and -B respectively. C-terminal chimerics A402B and B393A were made by exchanging amino acid segments 403-527 and 394-520 of MAO-A and -B respectively, and internal chimerics AB161-375A and BA152-366B 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.
authors.affiliation: Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Shih
authors.forename: K
authors.initials: K
authors.lastname: Chen
authors.forename: R M
authors.initials: RM
authors.lastname: Geha
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D003010:Clorgyline / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008995:Monoamine Oxidase / Q000737:chemistry* / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012642:Selegiline / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D014162:Transfection
chemical_list: D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D011993:Recombinant Fusion Proteins; D012642:Selegiline; D008995:Monoamine Oxidase; D003010:Clorgyline