CLONING OF THE GLUCOSE-6-PHOSPHATE-DEHYDROGENASE GENE FROM PLASMODIUM-FALCIPARUM

Glucose 6-phosphate dehydrogenase (G6PD) deficiency is one of the huma n genetic traits that confer relative resistance against malaria cause d by Plasmodium falciparum. It has been previously shown that this org anism, during its intraerythrocytic development, produces its own G6PD , which has properties different from those of human G6PD. In order to investigate the role of this enzyme in parasite-host cell interaction s, we have isolated the G6PD gene from Plasmodium falciparum as a set of overlapping lambda gt11 clones. By sequence analysis we have found a single open reading frame, uninterrupted by introns, coding for a pr otein of 910 amino acids, almost twice as long as any previously seque nced G6PD molecule. The P. falciparum G6PD mRNA is 5.1 kb in size and has an exceptionally long 5' untranslated region of some 1000 nucleoti des. We have mapped the G6PD gene to chromosome 14. The C-terminal por tion of the predicted protein, from amino acid 310-910 (except for an 'insert' of 62 amino acids), has 39% homology to human G6PD, with a nu mber of characteristic, fully conserved peptides. The N-terminal porti on of the predicted protein has no homology to G6PD, but it contains a peptide in which 7 out of 12 amino acids are identical to the putativ e glutathione binding site of human glutathione S-transferase.