Abstract
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.
Original language | English |
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Pages (from-to) | 97-110 |
Number of pages | 14 |
Journal | Proteins: Structure, Function and Genetics |
Volume | 32 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Jul 1998 |
Keywords
- Flavoproteins
- Fold prediction
- Knowledge-based modeling
- MAO A
- Membrane protein
- Secondary structure
- Threading
- Type A monoamine oxidase