Glutathione-dependent activities of Trypanosoma cruzi p52 makes it a new member of the thiol:disulphide oxidoreductase family.
Trypanothione: glutathione disulphide thioltransferase of Try-panosoma cruzi (p52) is a key enzyme in the regulation of the intracellular thiol-disulphide redox balance by reducing glutathione disulphide. Here we show that p52, like other disulphide oxidoreductases possessing the CXXC active site motif, catalyses the reduction of low-molecular-mass disulphides (hydroxyethyl-disulphide) as well as protein disulphides (insulin). However, p52 seems to be a poor oxidase under physiological conditions as evidenced by its very low rate for oxidative renaturation of reduced ribonuclease A Like thioltransferase and protein disulphide isomerase, p52 was found to possess a glutathione-dependent dehydroascorbate reductase activity. The kinetic parameters were in the same range as those determined for mammalian dehydroascorbate reductases. A catalytic mechanism taking into account both trypanothione- and glutathione-dependent reduction reactions was proposed. This newly characterized enzyme is specific for the parasite and provides a new target for specific chemotherapy.
Moutiez
M
M
Service de Chimie des biomolécules, URA CNRS 1309, Institut Pasteur de Lille, France.
Quéméneur
E
E
Sergheraert
C
C
Lucas
V
V
Tartar
A
A
Davioud-Charvet
E
E
D000818:Animals; D002384:Catalysis; D004220:Disulfides / Q000378:metabolism; D004789:Enzyme Activation; D005978:Glutathione / Q000502:physiology*; D007328:Insulin / Q000378:metabolism; D007535:Isomerases / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D019704:Protein Disulfide-Isomerases; D013379:Substrate Specificity; D014349:Trypanosoma cruzi / Q000201:enzymology*
D004220:Disulfides; D007328:Insulin; D010088:Oxidoreductases; C020666:glutathione dehydrogenase (ascorbate); D007535:Isomerases; D019704:Protein Disulfide-Isomerases; D005978:Glutathione