The putative glutathione peroxidase gene of Plasmodium falciparum codes for a thioredoxin peroxidase

A putative glutathione peroxidase gene (Swiss-Prot accession number Z 68200 ) of Plasmodium falciparum, the causative agent of tropical malaria, was ex pressed in Escherichia coli and purified to electrophoretic homogeneity, Li ke phospholipid hydroperoxide glutathione peroxidase of mammals, it proved to be monomeric, It was active with H2O2 and organic hydroperoxides but, un like phospholipid hydroperoxide glutathione peroxidase, not with phosphatid ylcholine hydroperoxide, With glutathione peroxidases it shares the ping po ng mechanism with infinite V-max and K-m when analyzed with GSH as substrat e, As a homologue with selenocysteine replaced by cysteine, its reactions w ith hydroperoxides and GSH are 3 orders of magnitude slower than those of t he selenoperoxidases, Unexpectedly, the plasmodial enzyme proved to react f aster with thioredoxins than with GSH and most efficiently with thioredoxin of P. falciparum (Swiss-Prot accession number 202664), It is therefore rec lassified as thioredoxin peroxidase. With plasmodial thioredoxin, the enzym e also displays ping-pong kinetics, yet with a limiting K-m of 10 muM and a k(1)' of 0.55 s(-1). The apparent k(1)' for oxidation with cumene, t-butyl , and hydrogen peroxides are 2.0 x 10(4) M-1 s(-1) 3.3 x 10(3) M-1 s(-1), a nd 2.5 x 10(3) M-1 s(-1) respectively. k(2)' for reduction by autologous th ioredoxin is 5.4 x 10(4) M-1 s(-1) (21.2 M-1 s(-1) for GSH), The newly disc overed enzymatic function of the plasmodial gene product suggests a reconsi deration of its presumed role in parasitic antioxidant defense.