title: Conserved elements of the cytochrome P-450 superfamily found in monoamine oxidase B.
abstract: Monoamine oxidases A and B (MAO A and B) are the major enzymes in mammals that catalyze the oxidative deamination or oxidation of neurotransmitters, peripheral vasoactive amines, and xenobiotics (e.g. MPTP). Although these enzymes are among the most widely studied flavoproteins, their integral association with the outer mitochondrial membrane has deterred knowledge of their structures until recent work yielded the three-dimensional structure of MAO B [Nat. Struct. Biol. 9 (2002) 22]. In our study, we compared the primary sequence in different regions of MAO B to those in selected proteins of known structure, including cytochrome P-450. Using site-directed mutagenesis [Prog. Nucleic Acid Res. Mol. Biol. 65 (2001) 129], we have identified three amino acids residues (Phe 423, Glu 427, and Thr 428) that appear to play a role in generating catalytically active MAO B. However, examination of models of the MAO B structure show that these residues lie outside the substrate binding site. Thus, it appears that Phe 423, Glu 427 and Thr 428 do not directly affect the active site, but they could modulate activity through an independent function such as non-covalent binding of FAD during synthesis of the MAO B polypeptide chain.
authors.affiliation: Division of Medicinal Chemistry, College of Pharmacy, The Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Duane A
authors.initials: DA
authors.lastname: Lewis
authors.forename: Kevin N
authors.initials: KN
authors.lastname: Dalby
authors.forename: Creed W
authors.initials: CW
authors.lastname: Abell
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D019556:COS Cells; D002522:Chlorocebus aethiops; D017124:Conserved Sequence / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D008995:Monoamine Oxidase / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: D003577:Cytochrome P-450 Enzyme System; D008995:Monoamine Oxidase