Al Claiborne
Gram-positive bacteria such as the streptococci present an intriguing system for investigating the structural, functional, and genetic aspects of oxygen metabolism. These facultative anaerobes lack the ability to synthesize heme and therefore do not have either catalase or the respiratory cytochromes found in other bacteria such as Escherichia coli. In place of these hemeproteins, streptococci have developed an unusual array of flavin-linked enzymatic responses to the presence of oxygen and its metabolites; these include the NADH peroxidase and NADH oxidase, which have been studied intensively in our laboratory. The combined application of molecular cloning approaches with X-ray crystallography and functional analyses has allowed us to demonstrate that these proteins represent a new class of peroxide reductases within the flavoprotein disulfide reductase family. A major distinction between the peroxide and disulfide reductase classes lies in the unique cysteine-sulfenic acid (Cys-SOH) redox center identified in the peroxidase and oxidase, in contrast to the redox-active disulfides (Cys-SS-Cys) found in most disulfide reductases. Our laboratory is currently applying technologies spanning the range from site-directed mutagenesis to rapid reaction kinetics and crystallography in the study of the peroxidase and oxidase. In connection with these studies, we are also investigating the unique coenzyme A-disulfide reductase from Staphylococcus aureus and the streptococcal alpha-glycerophosphate oxidase.
Stereo view of the superimposed active sites of the C44S mutant of Streptococcus pyogenes NADH oxidase (Nox; Mallett TC, Sakai H, Parsonage D, Claiborne A, and Tsukihara T) and the wild-type NA DH peroxidase (Npx; Yeh JI, Parsonage D, and Claiborne A).
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