Conversion of a peroxiredoxin into a disulfide reductase by a triplet repeat expansion.
Pathways for the reduction of protein disulfide bonds are found in all organisms and are required for the reductive recycling of certain enzymes including the essential protein ribonucleotide reductase. An Escherichia coli strain that lacks both thioredoxin reductase and glutathione reductase grows extremely poorly. Here, we show that a mutation occurring at high frequencies in the gene ahpC, encoding a peroxiredoxin, restores normal growth to this strain. This mutation is the result of a reversible expansion of a triplet nucleotide repeat sequence, leading to the addition of one amino acid that converts the AhpC protein from a peroxidase to a disulfide reductase. The ready mutational interconversion between the two activities could provide an evolutionary advantage to E. coli.
Ritz
D
D
Department of Microbiology and Molecular Genetics, 200 Longwood Avenue, Harvard Medical School, Boston, MA, 02115, USA.
Lim
J
J
Reynolds
C M
CM
Poole
L B
LB
Beckwith
J
J
D000595:Amino Acid Sequence; D001483:Base Sequence; D001555:Benzene Derivatives / Q000494:pharmacology; D001665:Binding Sites; D005075:Biological Evolution; D004268:DNA-Binding Proteins; D004220:Disulfides / Q000378:metabolism*; D004228:Dithionitrobenzoic Acid / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029968:Escherichia coli Proteins; D005798:Genes, Bacterial; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009243:NAD / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D009876:Operon; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010544:Peroxidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D010545:Peroxides / Q000378:metabolism; D054464:Peroxiredoxins; D010641:Phenotype; D012097:Repressor Proteins / Q000378:metabolism; D013489:Suppression, Genetic; D014157:Transcription Factors / Q000378:metabolism; D014169:Transformation, Bacterial; D019680:Trinucleotide Repeat Expansion
D001555:Benzene Derivatives; D004268:DNA-Binding Proteins; D004220:Disulfides; D029968:Escherichia coli Proteins; D010545:Peroxides; D012097:Repressor Proteins; D014157:Transcription Factors; C499299:oxyR protein, E coli; D009243:NAD; D004228:Dithionitrobenzoic Acid; D006861:Hydrogen Peroxide; D010544:Peroxidases; D054464:Peroxiredoxins; C515937:ahpC protein, E coli; D009247:NADH, NADPH Oxidoreductases; C014703:disulfide reductase (NADH); D005978:Glutathione; C007164:cumene hydroperoxide