ジャーナル: PLoS Biol / 年: 2021 タイトル: Structural characterization of the Plasmodium falciparum lactate transporter PfFNT alone and in complex with antimalarial compound MMV007839 reveals its inhibition mechanism. 著者: Xi Peng / Nan Wang / Angqi Zhu / Hanwen Xu / Jialu Li / Yanxia Zhou / Chen Wang / Qingjie Xiao / Li Guo / Fei Liu / Zhi-Jun Jia / Huaichuan Duan / Jianping Hu / Weidan Yuan / Jia Geng / ...著者: Xi Peng / Nan Wang / Angqi Zhu / Hanwen Xu / Jialu Li / Yanxia Zhou / Chen Wang / Qingjie Xiao / Li Guo / Fei Liu / Zhi-Jun Jia / Huaichuan Duan / Jianping Hu / Weidan Yuan / Jia Geng / Chuangye Yan / Xin Jiang / Dong Deng / 要旨: 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 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.