The proposed work focuses on three molybdenum-containing enzymes of environmental relevance: DMSO reductase, arsenite oxidase and sulfite oxidase. The first of these catalyzes the reduction of DMSO to the anti-greenhouse gas DIMS, and as such plays an important role not simply in the global sulfur cycle but in modulating climate as well. The second enzyme catalyzes the oxidation of arsenite to arsenate, an important step in the biotransformation of arsenic in the environment that represents a detoxification mechanism for those microorganisms in which it is found. It is a member of the same family of molybdenum-containing enzymes as DMSO reductase, but has an active site structure that represents a variation on that seen in DMSO reductase. Sulfite oxidase from higher eukaryotes (both vertebrates and plants) catalyzes the final step in sulfur catabolism, the oxidation of sulfite to sulfate, and prevents the deleterioius accumulation of the highly reactive sulfite in vivo. The overall goal of the proposed work is to gain a more complete understanding of the mechanism of action of these enzymes in the context of their structures, comparing and contrasting their behavior. The guiding hypothesis behind the approach is that enzyme function and catalytic power are dictated by the physical and electronic structure of the active site.
The Specific Aims i nclude rapid kinetic studies as well as spectroscopic and computational work aimed at determining the electronic structures of the enzyme active sites. In the cases of DMSO reductase and sulfite oxidase, site-directed mutants targeting specific active site amino acid residues will also be examined to evaluate their roles in catalysis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
1R01ES012658-01A2
Application #
6916855
Study Section
Metallobiochemistry Study Section (BMT)
Program Officer
Balshaw, David M
Project Start
2005-09-01
Project End
2010-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
1
Fiscal Year
2005
Total Cost
$343,306
Indirect Cost
Name
Ohio State University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
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