Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02011 (FAD)
 5,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monoamine oxidases, type A and type B, are principal enzymes for the degradation of biogenic amines, including catecholamines and serotonin. These isozymes have been implicated in neuropsychiatric disorders. Previously, cDNA clones for both MAO-A and MAO-B have been sequenced and the genes encoding them have been localized to human chromosome Xp11.23-Xp11.4. In this work, we isolated human genomic clones spanning almost all the MAOA gene from cosmid and phage libraries using a cDNA probe for MAO-A. Restriction mapping and sequencing show that the human MAOA gene extends over 70 kb and is composed of 15 exons. The exon structure of human MAOA is similar to that described by others for human MAOB. Exon 12 (bearing the codon for cysteine, which carries the covalently bound FAD cofactor) and exon 13 are highly conserved between human MAOA and MAOB genes (92% at the amino acid level). Earlier work revealed two species of MAO-A mRNA, 2.1 kb and 4.5-5.5 kb. We now report on further cDNA isolation and sequencing, which demonstrates that the longer message has an extension of 2.2 kb in the 3' noncoding region. This extended region is contained entirely within exon 15. The two messages therefore appear to be generated by the use of two alternative polyadenylation sites. Results from the present work should facilitate the mutational analysis of functional domains of MAO-A and MAO-B. Knowledge of the gene structure will also help in evaluating the role of genetic variations in MAO-A in human disease through the use of genomic DNA, which is more accessible than the RNA, as a template for PCR-amplification and sequencing.
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PMID:Structure of the human gene for monoamine oxidase type A. 188 75

Monoamine oxidases A and B [MAOA and MAOB; amine:oxygen oxidoreductase (deaminating) (flavin-containing), EC 1.4.3.4] play important roles in the metabolism of neuroactive, vasoactive amines and the Parkinsonism-producing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Human MAOA and MAOB genes isolated from X chromosome-specific libraries span at least 60 kilobases, consist of 15 exons, and exhibit identical exon-intron organization. Exon 12 codes for the covalent FAD-binding-site and is the most conserved exon; the MAOA and MAOB exon 12 products share 93.9% peptide identity. These results suggest that MAOA and MAOB are derived from duplication of a common ancestral gene and provide insight on the structural/functional relationship of the enzyme products.
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PMID:Human monoamine oxidase A and B genes exhibit identical exon-intron organization. 202 12

Monoamine oxidase (MAO) is an FAD-containing mitochondrial outer-membrane protein which catalyzes the degradation of several neurotransmitters in the central nervous system. The two subtypes of MAO, MAOA and MAOB, have similar primary sequences but different substrate and inhibitor specificities. The structure of human MAOB has recently been determined, but the structure of MAOA remains unknown. To clarify the mechanisms underlying their unique substrate and inhibitor recognition and thereby facilitate the development of new specific inhibitors to treat MAO-related neurological disorders, rat MAOA was crystallized in a complex with the specific inhibitor clorgyline. Diffraction data were collected to 3.2 A resolution. The crystal belongs to the space group P4(3)2(1)2, with unit-cell parameters a = b = 158.2, c = 258.4 A.
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PMID:Crystallization and preliminary crystallographic analysis of rat monoamine oxidase A complexed with clorgyline. 1474 10

The high level expression and purification of rat monoamine oxidase B (rMAOB) in the methylotrophic yeast Pichia pastoris is reported. Nearly 100 mg of purified rMAOB is obtained from 130 g (wet weight) of cells (0.5 L of culture). The MALDI-TOF mass spectrum of the purified protein shows a single species with a molecular mass of 59.228 +/- 0.064 kDa, which agrees with the calculated molecular weight of 59.172 kDa for the rMAOB protein sequence assuming one mole of covalent FAD per mole of the enzyme. Consistent with the MALDI-MS data, purified rMAOB shows a single band near 60 kDa in Coomassie-stained SDS-PAGE gel as well as on Western blot analyses performed using antisera raised against human MAOA and BSA-conjugated FAD. A partial amino acid sequence of the purified protein is confirmed to be that of the wild type rMAOB by in-gel trypsin digestion and MALDI-TOF-MS analyses of the liberated peptide fragments. Steady state kinetic data show that purified rMAOB exhibits a K(m)(amine) of 176 +/- 15 microM and a k(cat) of 497 +/- 83 min(-1) for benzylamine oxidation, and a K(m)(O2) of 170 +/- 10 microM. Kinetic parameters obtained for purified rMAOB are compared with those reported earlier for recombinant human liver MAOB expressed in P. pastoris.
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PMID:Characterization of detergent purified recombinant rat liver monoamine oxidase B expressed in Pichia pastoris. 1842 70