In:
PLOS Biology, Public Library of Science (PLoS), Vol. 19, No. 9 ( 2021-9-9), p. e3001386-
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.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001386
DOI:
10.1371/journal.pbio.3001386.g001
DOI:
10.1371/journal.pbio.3001386.g002
DOI:
10.1371/journal.pbio.3001386.g003
DOI:
10.1371/journal.pbio.3001386.g004
DOI:
10.1371/journal.pbio.3001386.g005
DOI:
10.1371/journal.pbio.3001386.g006
DOI:
10.1371/journal.pbio.3001386.s001
DOI:
10.1371/journal.pbio.3001386.s002
DOI:
10.1371/journal.pbio.3001386.s003
DOI:
10.1371/journal.pbio.3001386.s004
DOI:
10.1371/journal.pbio.3001386.s005
DOI:
10.1371/journal.pbio.3001386.s006
DOI:
10.1371/journal.pbio.3001386.s007
DOI:
10.1371/journal.pbio.3001386.s008
DOI:
10.1371/journal.pbio.3001386.s009
DOI:
10.1371/journal.pbio.3001386.s010
DOI:
10.1371/journal.pbio.3001386.s011
DOI:
10.1371/journal.pbio.3001386.s012
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2126773-X
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