Structural properties of human monoamine oxidases A and B

The structural elucidations of human monoamine oxidases A and B (MAO-A and -B) have provided novel insights into their similarities and differences. Although the enzymes exhibit ∼70% sequence identities, highly conserved chain folds, and are structurally identical in their flavin adenine dinucleotide (FAD)-binding sites, they differ considerably in the structures of their active sites opposite the flavin cofactor. MAO-A has a monopartite cavity of ∼550Å(3), and MAO-B exhibits a bipartite cavity structure with an entrance cavity of 290Å(3) and a substrate cavity of ∼400Å(3). Ile199 functions as a conformational "gate" separating the two cavities. Both enzymes are anchored to the outer mitochondrial membrane via C-terminal helical tails. Loop structures are found at the entrances to their active sites at the membrane surface. Although the crystal structure of human MAO-A is monomeric while MAO-B is dimeric, both enzymes are dimeric in their membrane-bound forms. Dimerization may be important for the favorable orientation of the resultant protein dipole moment toward the anionic membrane surface.