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- PDB-7e26: Structure of PfFNT in apo state -

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Basic information

Entry
Database: PDB / ID: 7.0E+26
TitleStructure of PfFNT in apo state
ComponentsFormate-nitrite transporter
KeywordsTRANSPORT PROTEIN / Lactate / transporter
Function / homology
Function and homology information


high-affinity secondary active nitrite transmembrane transporter activity / lactate transmembrane transport / nitrite transport / lactate:proton symporter activity / membrane
Similarity search - Function
Formate and nitrite transporters signature 2. / Formate/nitrite transporter / Formate/nitrite transporter, conserved site / Formate/nitrite transporter / Aquaporin-like
Similarity search - Domain/homology
Formate-nitrite transporter
Similarity search - Component
Biological speciesPlasmodium falciparum 3D7 (eukaryote)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.29 Å
AuthorsYan, C.Y. / Jiang, X. / Deng, D. / Peng, X. / Wang, N. / Zhu, A. / Xu, H. / Li, J.
CitationJournal: PLoS Biol / Year: 2021
Title: Structural characterization of the Plasmodium falciparum lactate transporter PfFNT alone and in complex with antimalarial compound MMV007839 reveals its inhibition mechanism.
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 / ...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 /
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.
History
DepositionFeb 4, 2021Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Aug 18, 2021Provider: repository / Type: Initial release
Revision 1.1Mar 2, 2022Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2May 17, 2023Group: Structure summary / Category: audit_author

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Assembly

Deposited unit
D: Formate-nitrite transporter
A: Formate-nitrite transporter
B: Formate-nitrite transporter
C: Formate-nitrite transporter
E: Formate-nitrite transporter


Theoretical massNumber of molelcules
Total (without water)172,4615
Polymers172,4615
Non-polymers00
Water1,44180
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area23740 Å2
ΔGint-246 kcal/mol
Surface area45060 Å2

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Components

#1: Protein
Formate-nitrite transporter /


Mass: 34492.281 Da / Num. of mol.: 5
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Plasmodium falciparum 3D7 (eukaryote) / Strain: 3D7 / Gene: PF3D7_0316600 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: O77389
#2: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 80 / Source method: isolated from a natural source / Formula: H2O

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Pentameric complex of FNT / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Molecular weightValue: 0.17 MDa / Experimental value: YES
Source (natural)Organism: Plasmodium falciparum 3D7 (eukaryote)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

CTF correctionType: NONE
3D reconstructionResolution: 2.29 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 221350 / Symmetry type: POINT

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