EMD-30952

Single-particle
2.29 Å
EMD-30952 Deposition: 04/02/2021
Map released: 18/08/2021
Last modified: 05/06/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-30952

Structure of PfFNT in apo state

EMD-30952

Single-particle
2.29 Å
EMD-30952 Deposition: 04/02/2021
Map released: 18/08/2021
Last modified: 05/06/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Plasmodium falciparum 3D7
Sample: Pentameric complex of FNT
Fitted models: 7e26 (Avg. Q-score: 0.659)

Deposition Authors: Yan CY, Jiang X , Peng X, Wang N , Zhu A , Xu H , Li J
Structural characterization of the Plasmodium falciparum lactate transporter PfFNT alone and in complex with antimalarial compound MMV007839 reveals its inhibition mechanism.
Peng X, Wang N , Zhu A , Xu H , Li J , Zhou Y, Wang C, Xiao Q, Guo L, Liu F, Jia ZJ, Duan H, Hu J, Yuan W, Geng J, Yan C , Jiang X , Deng D
(2021) PLoS Biol , 19 , e3001386 - e3001386
PUBMED: 34499638
DOI: doi:10.1371/journal.pbio.3001386
ISSN: 1545-7885
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 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.