Copper-containing amine oxidases are widely distributed in nature and are involved in the metabolism of biogenic primary amines. Amine oxidases may have a variety of functions in the cardiovascular, gastrointestinal, and nervous systems of mammals. Amine oxidases are also responsible for the cross-linking of connective tissue structural proteins (elastin and collagen). It appears that numerous compounds with antifungal, antiprotozoal, or anticancer activities may target amine oxidases. For example pentamidine, a leading drug for the treatment of Pneumocystis carinii pneumonia (PCP) in AIDS patients belongs to class of compounds that inhibit amine oxidases. A major goal are to determine the 3-D structures of multiple amine oxidases, including human kidney diamine oxidase, which has been over-expressed and purified to homogeneity. Other major goals are to define the molecular bases for substrate specificity and selective inhibition among amine oxidases, and to elucidate the mechanisms of amine oxidation and cofactor (TPQ) biogenesis. In addition, the structure and biogenesis of a related enzyme, galactose oxidase, will be examined. Site-directed mutagenesis, spectroscopy, kinetics measurements, and crystallography are employed. Combining structural and mechanistic data will permit a detailed understanding of the structure and function of these important enzymes to be developed.
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