GLUTATHIONE-DEPENDENT ACTIVITIES OF TRYPANOSOMA-CRUZI P52 MAKES IT A NEW MEMBER OF THE THIOL-DISULFIDE OXIDOREDUCTASE FAMILY

Trypanothione: glutathione disulphide thioltransferase of Trypanosoma cruzi (p52) is a key enzyme in the regulation of the intracellular thi ol-disulphide redox balance by reducing glutathione disulphide. Here w e show that p52, like other disulphide oxidoreductases possessing the CXXC active site motif, catalyses the reduction of low-molecular-mass disulphides (hydroxyethyldisulphide) as well as protein disulphides (i nsulin), However, p52 seems to be a poor oxidase under physiological c onditions as evidenced by its very low rate for oxidative renaturation of reduced ribonuclease A, Like thioltransferase and protein disulphi de isomerase, p52 was found to possess a glutathione-dependent dehydro ascorbate 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 gluta thione-dependent reduction reactions was proposed. This newly characte rized enzyme is specific for the parasite and provides a new target fo r specific chemotherapy.