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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM027659-23S1
Application #
6652343
Study Section
Physical Biochemistry Study Section (PB)
Program Officer
Preusch, Peter C
Project Start
1980-07-01
Project End
2005-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
23
Fiscal Year
2002
Total Cost
$66,979
Indirect Cost
Name
Montana State University Bozeman
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
City
Bozeman
State
MT
Country
United States
Zip Code
59717
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Rogers, Melanie S; Hurtado-Guerrero, Ramon; Firbank, Susan J et al. (2008) Cross-link formation of the cysteine 228-tyrosine 272 catalytic cofactor of galactose oxidase does not require dioxygen. Biochemistry 47:10428-39
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