title: Glutathione-dependent activities of Trypanosoma cruzi p52 makes it a new member of the thiol:disulphide oxidoreductase family.
abstract: 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.
authors.affiliation: Service de Chimie des biomolécules, URA CNRS 1309, Institut Pasteur de Lille, France.
authors.forename: M
authors.initials: M
authors.lastname: Moutiez
authors.forename: E
authors.initials: E
authors.lastname: Quéméneur
authors.forename: C
authors.initials: C
authors.lastname: Sergheraert
authors.forename: V
authors.initials: V
authors.lastname: Lucas
authors.forename: A
authors.initials: A
authors.lastname: Tartar
authors.forename: E
authors.initials: E
authors.lastname: Davioud-Charvet
mesh_terms: 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*
chemical_list: D004220:Disulfides; D007328:Insulin; D010088:Oxidoreductases; C020666:glutathione dehydrogenase (ascorbate); D007535:Isomerases; D019704:Protein Disulfide-Isomerases; D005978:Glutathione