The principal objective of this project is to understand in detail the mechanisms whereby Zn/Cu, Fe, and Mn containing superoxide dismutases catalyze the reaction, 202-+2H+ is greater than H2O2+O2. Our procedures involve the application of a variety of physical techniques ranging from x-ray crystallography to obtain three-dimensional structures to spectroscopic measuements to characterize the electronic structure of these metalloproteins. Kinetic mechanisms are being explored using a stopped-flow spectrophotometer specially designed for the study of superoxide in aqueous media. Simple recombinant DNA technqiues are being applied to the study of enzyme mechanisms and physiological function of these proteins.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM035189-05S1
Application #
3287507
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1984-12-01
Project End
1990-06-30
Budget Start
1989-12-01
Budget End
1990-06-30
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Los Alamos National Lab
Department
Type
Organized Research Units
DUNS #
City
Los Alamos
State
NM
Country
United States
Zip Code
87545
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Brown, O R; Smyk-Randall, E; Draczynska-Lusiak, B et al. (1995) Dihydroxy-acid dehydratase, a [4Fe-4S] cluster-containing enzyme in Escherichia coli: effects of intracellular superoxide dismutase on its inactivation by oxidant stress. Arch Biochem Biophys 319:10-22
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Stallings, W C; Metzger, A L; Pattridge, K A et al. (1991) Structure-function relationships in iron and manganese superoxide dismutases. Free Radic Res Commun 12-13 Pt 1:259-68
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Niederhoffer, E C; Fee, J A (1990) Novel effect of aromatic compounds on the iron-dependent expression of the Escherichia coli K12 manganese superoxide dismutase (sodA) gene. Biol Met 3:237-41
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Fee, J A; Bull, C (1986) Steady-state kinetic studies of superoxide dismutases. Saturative behavior of the copper- and zinc-containing protein. J Biol Chem 261:13000-5