Glucose 6-phosphate dehydrogenase 6-phosphogluconolactonase: a unique bifunctional enzyme from Plasmodium falciparum

Esther Jortzik , Boniface Mwongela Mailu , Janina Preuss , Marina Fischer , Lars Bode , Stefan Rahlfs , K Becker (1)

1 Interdiscipinary Research Center

The survival of malaria parasites in human erythrocytes depends on the pentose phosphate pathway both in Plasmodium falciparum and its human host. Glucose 6-phosphate dehydrogenase (G6PD) deficiency, the most common human enzyme deficiency, leads to a lack of NADPH in erythrocytes, and protects from malaria. In Plasmodium falciparum, G6PD is combined with the second enzyme of the pentose phosphate pathway to a unique bifunctional enzyme named glucose 6-phosphate dehydrogenase 6-phosphogluconolactonase (GluPho). Here, we report for the first time the cloning, heterologous overexpression, purification, and kinetic characterization of both enzymatic activities of full length PfGluPho, and demonstrate striking structural and functional differences to the human enzymes. Detailed kinetic analyses indicate that PfGluPho functions on the basis of a rapid equilibrium random bi bi mechanism, where the binding of the second substrate depends on the first substrate. We furthermore show that PfGluPho is inhibited by S-glutathionylation. The availability of recombinant PfGluPho and the major differences to human G6PD facilitate studies on PfGluPho as an excellent drug target candidate in the search for new antimalarial drugs.

Mots clés: Life Sciences

Esther Jortzik, Boniface Mwongela Mailu, Janina Preuss, Marina Fischer, Lars Bode, et al.. Glucose 6-phosphate dehydrogenase 6-phosphogluconolactonase: a unique bifunctional enzyme from Plasmodium falciparum. Biochemical Journal, 2011, 436 (3), pp.641-650. ⟨10.1042/BJ20110170⟩. ⟨hal-00596268⟩