Structural analysis of Plasmodium falciparum PfHPPK-DHPS protein in complex with antimalarial drug Sulfodoxine and C17 inhibitor

The malaria parasites Plasmodium falciparum (Pf) and Plasmodium virax (Pv) infect more than 400 million people leading to 0.3 million deaths per year (1). This public health issue is becoming even more urgent due to the appearance of drug-resistant strains to available anti-malaria drugs. This is the case of the sulfadoxine drug (SDX) that targets the enzyme 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase-dihydropteroate synthase (HPPK-DHPS). This protein is involved in the folate biosynthesis pathway, essential in DNA synthesis and cell division. Our goal is to structurally study the Plasmodium falciparum PfHPPK-DHPS enzyme in complex with Sulfodoxine and other inhibitors identified by our collaborators to elucidate their mechanism of action.