PLASMODIUM-FALCIPARUM GLUTATHIONE-REDUCTASE EXHIBITS SEQUENCE SIMILARITIES WITH THE HUMAN HOST ENZYME IN THE CORE STRUCTURE BUT DIFFERS AT THE LIGAND-BINDING SITES

The homodimeric flavoenzyme glutathione reductase (GR) which catalyzes the reduction of glutathione disulfide is a cornerstone of the malari a parasite antioxidant defense and repair mechanisms. Here we report o n the identification of the GR gene from Plasmodium falciparum. A 1.4- kb fragment of the gene was amplified by polymerase chain reaction (PC R), Using this PCR fragment as a probe a full length cDNA clone (2085 bp) was isolated from a P. falciparum gametocyte library. The deduced amino acid sequence of 541 residues shows an overall identity of 35% w hen compared to the human enzyme. Most amino acids of known function a re identical. However, notable differences between human and parasite protein occur in the glutathione-binding pocket (for instance, Glu374 instead of the expected basic residue) and at the intersubunit contact area. These regions are of particular interest since they represent b inding sites of known GR inhibitors. Consequently, parasite GR can ser ve as a target structure for the design of antimalarial drugs.