A unique thioredoxin of the parasitic nematode Haemonchus contortus with glutaredoxin activity.
The dependency of parasites on the cellular redox systems has led to their investigation as novel drug targets. Defence against oxidative damage is through the thioredoxin and glutathione systems. The classic thioredoxin is identified by the active site Cys-Gly-Pro-Cys (CGPC). Here we describe the identification of a unique thioredoxin in the parasitic nematode, Haemonchus contortus. This thioredoxin-related protein, termed HcTrx5, has an arginine in its active site (Cys-Arg-Ser-Cys; CRSC) that is not found in any other organism. Recombinant HcTrx5 was able to reduce the disulfide bond in insulin, and be regenerated by mammalian thioredoxin reductase with a K(m) 2.19+/-1.5 microM, similar to the classic thioredoxins. However, it was also able to reduce insulin when glutathione and glutathione reductase replaced the thioredoxin reductase. When coupled with H. contortus peroxiredoxin, HcTrx5 was active using either the thioredoxin reductase or the glutathione and glutathione reductase. HcTrx5 is expressed through the life cycle, with highest expression in the adult stage. The unique activity of this thioredoxin makes it a potential drug target for the control of this parasite.
Sotirchos
Irene M
IM
Institute for the Biotechnology of Infectious Diseases, University of Technology, Sydney, Broadway NSW, Australia.
Hudson
Amanda L
AL
Ellis
John
J
Davey
Mary W
MW
D020816:Amino Acid Motifs; D000818:Animals; D001120:Arginine; D020134:Catalytic Domain; D019610:Cytoprotection / Q000502:physiology; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D054477:Glutaredoxins / Q000737:chemistry / Q000378:metabolism*; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism*; D006189:Haemonchus / Q000254:growth & development / Q000378:metabolism*; D007328:Insulin / Q000737:chemistry / Q000378:metabolism*; D008018:Life Cycle Stages / Q000502:physiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D013379:Substrate Specificity; D013880:Thioredoxin-Disulfide Reductase / Q000737:chemistry / Q000378:metabolism; D013879:Thioredoxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes
D054477:Glutaredoxins; D007328:Insulin; D013879:Thioredoxins; D001120:Arginine; D013880:Thioredoxin-Disulfide Reductase; D005978:Glutathione