Abstract
Malaria is a devastating disease caused by a protozoan parasite. It affects over 300 million individuals and results in over 400 000 deaths annually, most of whom are young children under the age of five. Hexokinase, the first enzyme in glucose metabolism, plays an important role in the infection process and represents a promising target for therapeutic intervention. Here, cryo-EM structures of two conformational states of Plasmodium vivax hexokinase (PvHK) are reported at resolutions of ∼3 Å. It is shown that unlike other known hexokinase structures, PvHK displays a unique tetrameric organization (∼220 kDa) that can exist in either open or closed quaternary conformational states. Despite the resemblance of the active site of PvHK to its mammalian counterparts, this tetrameric organization is distinct from that of human hexokinases, providing a foundation for the structure-guided design of parasite-selective antimalarial drugs.
Highlights
Malaria is a devastating disease that ravages large parts of the developing world
Malaria is caused by protozoan parasites of the genus Plasmodium, of which P. falciparum and P. vivax are the two predominant species associated with disease mortality and morbidity (Naing et al, 2014; World Health Organization, 2018)
Given its essential role in glucose metabolism, Plasmodium hexokinase has been considered as a promising drug target (Davis et al, 2016; Harris et al, 2013)
Summary
Malaria is a devastating disease that ravages large parts of the developing world. It infects millions of individuals every year and kills hundreds of thousands, most of whom are children under the age of five (World Health Organization, 2018). Glycolysis inhibitors deplete parasite ATP (van Schalkwyk et al, 2008) Consistent with this hypothesis, many glucose analogs have been shown to have antiparasitic activity (Santos de Macedo et al, 2001; Udeinya & Van Dyke, 1981; van Schalkwyk et al, 2008)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
