+Open data
-Basic information
Entry | Database: PDB / ID: 7.0E+27 | ||||||
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Title | Structure of PfFNT in complex with MMV007839 | ||||||
Components | Formate-nitrite transporter | ||||||
Keywords | TRANSPORT 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 / plasma membrane Similarity search - Function | ||||||
Biological species | Plasmodium falciparum 3D7 (eukaryote) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.29 Å | ||||||
Authors | Yan, C.Y. / Jiang, X. / Deng, D. / Peng, X. / Wang, N. / Zhu, A. / Xu, H. / Li, J. | ||||||
Citation | Journal: 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 |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7e27.cif.gz | 249 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7e27.ent.gz | 204.6 KB | Display | PDB format |
PDBx/mmJSON format | 7e27.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7e27_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 7e27_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 7e27_validation.xml.gz | 40 KB | Display | |
Data in CIF | 7e27_validation.cif.gz | 57 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/e2/7e27 ftp://data.pdbj.org/pub/pdb/validation_reports/e2/7e27 | HTTPS FTP |
-Related structure data
Related structure data | 30953MC 7e26C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 34492.281 Da / Num. of mol.: 5 Source method: isolated from a genetically manipulated source Details: MMV007839 / Source: (gene. exp.) Plasmodium falciparum 3D7 (eukaryote) / Strain: 3D7 / Gene: PF3D7_0316600 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: O77389 #2: Chemical | ChemComp-HV6 / ( #3: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: PfFNT / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Plasmodium falciparum 3D7 (eukaryote) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: NONE |
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3D reconstruction | Resolution: 2.29 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 291994 / Symmetry type: POINT |