First partial three-dimensional model of human monoamine oxidase A.
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 alpha/beta domains (the FAD-binding N-terminal and central domains) and an alpha+beta 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.
Facultés Universitaires Notre Dame de la Paix, Namur, Belgium. johan.wouters@fundp.ac.be
J
J
Wouters
G
G
Baudoux
D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D005420:Flavoproteins / Q000737:chemistry; D006801:Humans; D008432:Mathematical Computing; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008995:Monoamine Oxidase / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017421:Sequence Analysis
D005420:Flavoproteins; D008995:Monoamine Oxidase