Structural basis of transport and inhibition of the Plasmodium falciparum transporter PfFNT.
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ABSTRACT:
SUBMITTER: Lyu M
PROVIDER: S-EPMC8647005 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
Publications
Structural basis of transport and inhibition of the Plasmodium falciparum transporter PfFNT.
Lyu Meinan M Su Chih-Chia CC Kazura James W JW Yu Edward W EW
EMBO reports 20211201 12
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Project description:Plasmodium falciparum, the deadliest causal agent of malaria, caused more than half of the 229 million malaria cases worldwide in 2019. The emergence and spreading of frontline drug-resistant Plasmodium strains are challenging to overcome in the battle against malaria and raise urgent demands for novel antimalarial agents. The P. falciparum formate-nitrite transporter (PfFNT) is a potential drug target due to its housekeeping role in lactate efflux during the intraerythrocytic stage. Targeting PfFNT, MMV007839 was identified as a lead compound that kills parasites at submicromolar concentrations. Here, we present 2 cryogenic-electron microscopy (cryo-EM) structures of PfFNT, one with the protein in its apo form and one with it in complex with MMV007839, both at 2.3 Å resolution. Benefiting from the high-resolution structures, our study provides the molecular basis for both the lactate transport of PfFNT and the inhibition mechanism of MMV007839, which facilitates further antimalarial drug design.
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