This award is aimed at the elucidation of the structure and function of CuZn superoxide dismutase (SOD) found in bacteria. The bacterial CuZnSODs are periplasmic and thus adapted for defense against extra cytoplasmic oxidative stress. The research will study the CuZnSOD in two bacteria, Caulobacter crescentus and Legionella pneumophilia. Their genes, which had been previously cloned and sequenced, will be mutagenized and reintroduced into the bacteria. Characterization of the mutant strains will yield general insights into the role of periplasmic protein in defense against oxygen toxicity. The enzymes will be over-expressed and crystallized. Collaborative efforts will be made to obtain their 3-dimensional structure by X-ray crystallography. The results will enhance our understanding of how living cells protect themselves against the toxic effects of superoxides which are produced in wide variety of metabolic reactions and which may be the cause of myriads of human diseases.
