The disulfide redox system of Schistosoma mansoni and the importance of a multifunctional enzyme, thioredoxin glutathione reductase.
Schistosoma mansoni, a causative agent of schistosomiasis, is a major cause of human morbidity in tropical countries. Adult schistosomes, which reside in the hepatic portal system, are exposed to reactive oxygen compounds through respiration and as a result of the host immune response. To minimize oxidative stress schistosomes must possess adequate mechanisms of detoxification. Major detoxification systems rely on reducing equivalents from the disulfide oxidoreductases glutathione and thioredoxin. Therefore, maintenance of adequate levels of these thiols in a reduced form is critical. Here we show that S. mansoni possess an unusual thiol redox system centered on thioredoxin glutathione reductase. This enzyme represents an unusual fusion of a pyridine nucleotide disulfide oxidoreductase with a redox active glutaredoxin extension. Furthermore, we predict that this is a selenocysteine protein. Immunoprecipitation, western blot and inhibitor studies show that this protein has thioredoxin reductase, glutathione reductase, and glutaredoxin activities. Most importantly, we show that thioredoxin glutathione reductase appears to be the major, if not the sole enzyme for these activities in adult worms, completely replacing thioredoxin reductase and glutathione reductase. This is the first example of an organism with a redox system based exclusively on thioredoxin glutathione reductase.
Alger
Heather M
HM
Department of Biological Sciences, Illinois State University, Normal, IL 61790-4120, USA.
Williams
David L
DL
D000595:Amino Acid Sequence; D000818:Animals; D001310:Auranofin / Q000494:pharmacology; D004220:Disulfides / Q000378:metabolism*; D054477:Glutaredoxins; D005980:Glutathione Reductase / Q000737:chemistry / Q000378:metabolism*; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases; D011506:Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012550:Schistosoma mansoni / Q000201:enzymology*; D017279:Selenocysteine / Q000235:genetics / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000737:chemistry / Q000378:metabolism*
D004220:Disulfides; D054477:Glutaredoxins; D015801:Helminth Proteins; D009097:Multienzyme Complexes; D011506:Proteins; D011994:Recombinant Proteins; D017279:Selenocysteine; D001310:Auranofin; D010088:Oxidoreductases; D009247:NADH, NADPH Oxidoreductases; C466433:thioredoxin glutathione reductase; D005980:Glutathione Reductase; D013880:Thioredoxin-Disulfide Reductase