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Open data
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Basic information
| Entry | Database: EMDB / ID: EMD-30952 | |||||||||
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| Title | Structure of PfFNT in apo state | |||||||||
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Keywords | Lactate / transporter / TRANSPORT PROTEIN | |||||||||
| Function / homology | Function and homology informationhigh-affinity secondary active nitrite transmembrane transporter activity / lactate transmembrane transport / nitrite transport / lactate:proton symporter activity / vacuolar membrane / plasma membrane Similarity search - Function | |||||||||
| Biological species | ![]() | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.29 Å | |||||||||
Authors | Yan CY / Jiang X / Peng X / Wang N / Zhu A / Xu H / Li J | |||||||||
Citation | Journal: PLoS Biol / Year: 2021Title: 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. | |||||||||
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Structure visualization
| Movie |
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| Structure viewer | EM map: SurfView Molmil Jmol/JSmol |
| Supplemental images |
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Downloads & links
-EMDB archive
| Map data | emd_30952.map.gz | 167.6 MB | EMDB map data format | |
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| Header (meta data) | emd-30952-v30.xml emd-30952.xml | 9.9 KB 9.9 KB | Display Display | EMDB header |
| Images | emd_30952.png | 64.4 KB | ||
| Filedesc metadata | emd-30952.cif.gz | 5 KB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-30952 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30952 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 7e26MC ![]() 7e27C M: atomic model generated by this map C: citing same article ( |
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| Similar structure data |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_30952.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.6746 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Pentameric complex of FNT
| Entire | Name: Pentameric complex of FNT |
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| Components |
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-Supramolecule #1: Pentameric complex of FNT
| Supramolecule | Name: Pentameric complex of FNT / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 170 KDa |
-Macromolecule #1: Formate-nitrite transporter
| Macromolecule | Name: Formate-nitrite transporter / type: protein_or_peptide / ID: 1 / Number of copies: 5 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 34.492281 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: MPPNNSKYVL DPVSIKSVCG GEESYIRCVE YGKKKAHYSN LNLLAKAILA GMFVGLCAHA SGIAGGLFYY HKLREIVGAS MSVFVYGFT FPIAFMCIIC TGSDLFTGNT LAVTMALYEK KVKLLDYLRV MTISLFGNYV GAVSFAFFVS YLSGAFTNVH A VEKNHFFQ ...String: MPPNNSKYVL DPVSIKSVCG GEESYIRCVE YGKKKAHYSN LNLLAKAILA GMFVGLCAHA SGIAGGLFYY HKLREIVGAS MSVFVYGFT FPIAFMCIIC TGSDLFTGNT LAVTMALYEK KVKLLDYLRV MTISLFGNYV GAVSFAFFVS YLSGAFTNVH A VEKNHFFQ FLNDIAEKKV HHTFVECVSL AVGCNIFVCL AVYFVLTLKD GAGYVFSVFF AVYAFAIAGY EHIIANIYTL NI ALMVNTK ITVYQAYIKN LLPTLLGNYI AGAIVLGLPL YFIYKEHYYN FERSKRDNND AQMKSLSIEL RN UniProtKB: Formate-nitrite transporter |
-Macromolecule #2: water
| Macromolecule | Name: water / type: ligand / ID: 2 / Number of copies: 80 / Formula: HOH |
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| Molecular weight | Theoretical: 18.015 Da |
| Chemical component information | ![]() ChemComp-HOH: |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 8 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | FEI TITAN KRIOS |
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| Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
| Startup model | Type of model: NONE |
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| Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.29 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 221350 |
| Initial angle assignment | Type: ANGULAR RECONSTITUTION |
| Final angle assignment | Type: ANGULAR RECONSTITUTION |
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