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Edmondson Laboratory

Dale E. Edmondson

Professor


Dale Edmondson

The research focus of this laboratory involves investigations of structure-function relationships in enzymes catalyzing oxidation-reduction reactions. Among the enzymes belonging to this class, particular emphasis is given to the flavoenzymes (containing vitamin B2 and including monoamine oxidases A and B )and the molybdenum hydroxylases (xanthine dehydrogenase). Several of these enzymes are important targets in the development of drug therapies such as antidepressants (monoamine oxidase). The approaches to study complex molecules such as those listed above involve chemical, biophysical, and biochemical approaches. Mechanistic approaches on monoamine oxidases include steady state and rapid reaction kinetic studies as well as kinetic isotope effect studies in which enzyme intermediates are observed using absorption stopped flow kinetics or trapped using rapid freeze-quench kinetic techniques and analyzed by ESR spectroscopy. Our work on xanthine dehydrogenase involves the structure of the molybdenum cofactor site and the mechanism of purine hydroxylation at the metal site in the enzyme. Approaches to this problem include isotopic labeling of the Mo center and to clone and develop an expression system for the gene encoding xanthine dehydrogenase from the bacterium Comamonas acidovorans. The monoamine oxidase A and B project involves structure-activity studies to probe the structure of the amine binding site and to probe the detailed mechanism of oxidative deamination of amine neurotransmitters. Current work involves the expression of human liver genes for both the A and B forms in the yeast Pichia pastoris. This permits high level enzyme expression in quantities required for detailed structural and mechanistic studies and will facilitate site-directed mutagenesis studies as probes of the substrate binding site and amino acid residues involved in catalysis. Information regarding the 14th Annual Amine Oxidase Workshop can be found at www.pmcol.ualberta.ca/ao2010.

Current Members of the Edmondson Lab

Contact Information



Department of Biochemistry
1510 Clifton Rd. NE
Atlanta, GA 30322

O. Wayne Rollins Center
4021 Office
4078 Lab
404.727.5972 (Office tel.)
404.727.5971 (Lab tel.)
404.727.2738 (Fax)
deedmon@emory.edu