Alkyl hydroperoxide reductase from Salmonella typhimurium. Sequence and homology to thioredoxin reductase and other flavoprotein disulfide oxidoreductases.
The DNA sequence of the Salmonella typhimurium ahp locus was determined. The locus was found to contain two genes that encode the two proteins (C22 and F52a) that comprise the S. typhimurium alkyl hydroperoxide reductase activity. The predicted sequence of the F52a protein component of the alkyl hydroperoxide reductase was found to be highly homologous to the Escherichia coli thioredoxin reductase protein (34% identity with many conservative substitutions). The homology was found to be particularly striking in the region containing the redox-active cysteines of the thioredoxin reductase molecule, and among the identities were the redox-active cysteines themselves. Aside from the strong similarity to thioredoxin reductase, overall homology between the F52a protein and other flavoprotein disulfide oxidoreductases such as glutathione reductase, dihydrolipoamide dehydrogenase, and mercuric reductase was found to be rather limited, and the conserved active site segment common to the three proteins was not observed within the F52a protein. However, three short segments that have been implicated in FAD and NAD binding were found to be conserved between the F52a protein and the other disulfide reductases. These results suggest that the alkyl hydroperoxide reductase is the second known member of a class of disulfide oxidoreductases which was represented previously by thioredoxin reductase alone; they also allow the putative assignment of several functional domains.
Division of Biochemistry and Molecular Biology, University of California, Berkeley 94720.
L A
LA
Tartaglia
G
G
Storz
M H
MH
Brodsky
A
A
Lai
B N
BN
Ames
D000595:Amino Acid Sequence; D001483:Base Sequence; D004269:DNA, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005420:Flavoproteins / Q000235:genetics*; D005980:Glutathione Reductase / Q000235:genetics; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics*; D010088:Oxidoreductases / Q000235:genetics*; D010544:Peroxidases; D054464:Peroxiredoxins; D010957:Plasmids; D015183:Restriction Mapping; D012486:Salmonella typhimurium / Q000201:enzymology / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics*
D004269:DNA, Bacterial; D005420:Flavoproteins; D010088:Oxidoreductases; D010544:Peroxidases; D054464:Peroxiredoxins; C021551:mercuric reductase; D009247:NADH, NADPH Oxidoreductases; D005980:Glutathione Reductase; D013880:Thioredoxin-Disulfide Reductase