Journal article

Plasmodium falciparum glucose-6-phosphate dehydrogenase 6-phosphogluconolactonase is a potential drug target

Stacey M Allen, Erin E Lim, Esther Jortzik, Janina Preuss, Hwa Huat Chua, James I MacRae, Stefan Rahlfs, Kristina Haeussler, Matthew T Downton, Malcolm J McConville, Katja Becker, Stuart A Ralph

FEBS JOURNAL | WILEY-BLACKWELL | Published : 2015

Abstract

The malarial parasite Plasmodium falciparum is exposed to substantial redox challenges during its complex life cycle. In intraerythrocytic parasites, haemoglobin breakdown is a major source of reactive oxygen species. Deficiencies in human glucose-6-phosphate dehydrogenase, the initial enzyme in the pentose phosphate pathway (PPP), lead to a disturbed redox equilibrium in infected erythrocytes and partial protection against severe malaria. In P. falciparum, the first two reactions of the PPP are catalysed by the bifunctional enzyme glucose-6-phosphate dehydrogenase 6-phosphogluconolactonase (PfGluPho). This enzyme differs structurally from its human counterparts and represents a potential ta..

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Grants

Awarded by Deutsche Forschungsgemeinschaft


Awarded by Australian National Health and Medical Research Council (NHMRC)


Awarded by NHRMC Career Development Fellowship


Funding Acknowledgements

The study was supported by the Deutsche Forschungsgemeinschaft (grant BE 1540/18-1 to KB and SR) and by an Australian National Health and Medical Research Council (NHMRC) grant (APP1006024). SAR is supported by a NHRMC Career Development Fellowship (APP1062504). MJM is an NHMRC Principal Research Fellow (APP566643). We thank Dr Simon Cobbold (University of Melbourne) for helpful discussions. The authors have no conflict of interest to declare.