Monoamine Oxidase
Created | Updated Apr 27, 2006
Monoamine Oxidase (MAO) is ~60-kDa (as a dimer) flavoprotein that is the number one target for development of anti-depressants and treatment of Parkinson’s and Alzheimer diseases because its ability to degrade neurotransmitters such as serotonin, norepinephrine, dopamine and phenylethylamine. As of the fact that the level of MAO increases with the age, designing irreversible inhibitors for this enzyme has been the major interest. MAO is an outer mitochondrial enzyme existing in two isoforms, A and B respectively. Despite their 70% sequence identity both enzymes show different properties. Main difference of these enzymes is the different inhibitor and substrate specificities. For instance, pargyline which is a specific inhibitor for MAO B, does not function in MAO A. Clorgyline instead, is the specific inhibitor for MAO A and shows no inhibition on MAO B.
As the name “flavoprotein” implicates, a covalently bound FAD (Flavin Adenine Dinucleotide) cofactor is present in either enzyme at the C8a-position to a cysteine chain and in the absence of FAD the inactive apoenzyme form of MAO is being produced. This suggests that the flavin incorporation is critical for the function of these proteins.
The solution of the crystal structure of human MAO B by Dr. Dale E. Edmondson and his colleagues brought excitement to the scientific community that works on MAO since it provides promising future work to identify many unknowns about this protein. These unknowns are the structural and detailed mechanistic information and further elucidation of the pharmacological necessitates for the rational design of enzyme inhibitors. At this point, the knowledge of the active site plays a very important role for the exploration and understanding of the requirements for an efficient drug design for these proteins
As the name “flavoprotein” implicates, a covalently bound FAD (Flavin Adenine Dinucleotide) cofactor is present in either enzyme at the C8a-position to a cysteine chain and in the absence of FAD the inactive apoenzyme form of MAO is being produced. This suggests that the flavin incorporation is critical for the function of these proteins.
The solution of the crystal structure of human MAO B by Dr. Dale E. Edmondson and his colleagues brought excitement to the scientific community that works on MAO since it provides promising future work to identify many unknowns about this protein. These unknowns are the structural and detailed mechanistic information and further elucidation of the pharmacological necessitates for the rational design of enzyme inhibitors. At this point, the knowledge of the active site plays a very important role for the exploration and understanding of the requirements for an efficient drug design for these proteins
