Journalartikel

Jahr der Veröffentlichung: 2011

Seiten: 641-650

Zeitschrift: Biochemical Journal

Bandnummer: 436

Heftnummer: 3

ISSN: 0264-6021

eISSN: 1470-8728

Open Access Status: Green

DOI Link: https://doi.org/10.1042/BJ20110170

Verlag: Portland Press

Abstract: 
The survival of malaria parasites in human RBCs (red blood cells) depends on the pentose phosphate pathway, both in Plasmodium falciparum and its human host. G6PD (glucose-6-phosphate dehydrogenase) deficiency, the most common human enzyme deficiency, leads to a lack of NADPH in erythrocytes, and protects from malaria. In P falciparum, G6PD is combined with the second enzyme of the pentose phosphate pathway to create a unique bifunctional enzyme named GluPho (glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase). In the present paper, we report for the first time the cloning, heterologous overexpression, purification and kinetic characterization of both enzymatic activities of full-length PfGluPho (P. falciparum GluPho), and demonstrate striking structural and functional differences with 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 hG6PD (human G6PD) facilitate studies on PfGluPho as an excellent drug target candidate in the search for new antimalarial drugs.

Harvard-Zitierstil: Jortzik, E., Mailu, B., Preuss, J., Fischer, M., Bode, L., Rahlfs, S., et al. (2011) Glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase: a unique bifunctional enzyme from Plasmodium falciparum, Biochemical Journal, 436(3), pp. 641-650. https://doi.org/10.1042/BJ20110170

APA-Zitierstil: Jortzik, E., Mailu, B., Preuss, J., Fischer, M., Bode, L., Rahlfs, S., & Becker, K. (2011). Glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase: a unique bifunctional enzyme from Plasmodium falciparum. Biochemical Journal. 436(3), 641-650. https://doi.org/10.1042/BJ20110170