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First partial three‐dimensional model of human monoamine oxidase A
Author(s) -
Wouters Johan,
Baudoux Guy
Publication year - 1998
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(19980701)32:1<97::aid-prot11>3.0.co;2-i
Subject(s) - monoamine oxidase , flavin group , monoamine neurotransmitter , chemistry , biochemistry , cofactor , mutagenesis , stereochemistry , cysteine , biophysics , enzyme , biology , serotonin , receptor , mutation , gene
A survey of the major known structural aspects of monoamine oxidase (MAO) is given and a first partial model of human MAO A is presented. This 3D model has been established using secondary structure predictions and fold recognition methods. It shows two α/β domains (the FAD‐binding N‐terminal and central domains) and an α+β domain. The C‐terminal region is predicted to be responsible for anchoring the protein into the mitochondrial membrane and was not modeled. The covalent binding of the flavin cofactor to a cysteine residue is well predicted. The model is validated with experimental data from the literature and should be useful in designing new experimental studies (site‐directed mutagenesis, chemical modification, specific antibodies). This first step towards the 3D structure of monoamine oxidase should contribute to a better understanding of the mechanisms of action and inhibition of this drug target in the treatment of clinical depression. Proteins 32:97–110, 1998. © 1998 Wiley‐Liss, Inc.