RECOMBINANT PLASMODIUM-FALCIPARUM GLUTATHIONE-REDUCTASE IS INHIBITED BY THE ANTIMALARIAL DYE METHYLENE-BLUE

Plasmodium falciparum glutathione reductase (PfGR) has emerged as a dr ug target against tropical malaria, Here me report the expression of P fGR in Escherichia coli SG5(DE3) and isolation procedures for this pro tein. Recombinant PfGR does not differ from the authentic enzyme in it s enzymic properties, the turnover number being 9900 min(-1), The dime ric flavoenzyme exhibits redox-dependent absorption spectra; the singl e tryptophan residue (per 57.2 kDa subunit) is strongly fluorescent. P fGR can be inhibited by the antimalarial drug methylene blue at therap eutic concentrations; the K-i for non-competitive inhibition is 6.4 mu M. The sensitivity to methylene blue is observed also at high ionic s trength so that, by analogy to human GR, analysis of crystalline enzym e-drug complexes can be envisaged. (C) 1998 Federation of European Bio chemical Societies.