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Title | Structural characterization of the Plasmodium falciparum lactate transporter PfFNT alone and in complex with antimalarial compound MMV007839 reveals its inhibition mechanism. |
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Journal, issue, pages | PLoS Biol, Vol. 19, Issue 9, Page e3001386, Year 2021 |
Publish date | Sep 9, 2021 |
Authors | 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 / |
PubMed Abstract | 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. |
External links | PLoS Biol / PubMed:34499638 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.29 Å |
Structure data | EMDB-30952, PDB-7e26: EMDB-30953, PDB-7e27: |
Chemicals | ChemComp-HOH: ChemComp-HV6: |
Source |
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Keywords | TRANSPORT PROTEIN / Lactate / transporter / lactate transporter |