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- EMDB-24076: Cryo-EM structure of PfFNT-inhibitor complex -

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Basic information

Entry
Database: EMDB / ID: EMD-24076
TitleCryo-EM structure of PfFNT-inhibitor complex
Map data
Sample
  • Complex: PfFNT-inhibitor complex
    • Protein or peptide: Formate-nitrite transporter
  • Ligand: (Z)-4,4,5,5,5-pentakis(fluoranyl)-1-(4-methoxy-2-oxidanyl-phenyl)-3-oxidanyl-pent-2-en-1-one
  • Ligand: water
KeywordsPfFNT / Lactate transporter / PfFNT-MMV007839 complex / TRANSPORT PROTEIN-INHIBITOR complex
Function / homology
Function and homology information


high-affinity secondary active nitrite transmembrane transporter activity / lactate transmembrane transport / nitrite transport / lactate:proton symporter activity / vacuolar membrane / plasma 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) / Plasmodium falciparum (isolate 3D7) (eukaryote)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.18 Å
AuthorsYu EW / Su C
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID) United States
CitationJournal: EMBO Rep / Year: 2021
Title: Structural basis of transport and inhibition of the Plasmodium falciparum transporter PfFNT.
Authors: Meinan Lyu / Chih-Chia Su / James W Kazura / Edward W Yu /
Abstract: The intra-erythrocyte stage of P. falciparum relies primarily on glycolysis to generate adenosine triphosphate (ATP) and the energy required to support growth and reproduction. Lactic acid, a ...The intra-erythrocyte stage of P. falciparum relies primarily on glycolysis to generate adenosine triphosphate (ATP) and the energy required to support growth and reproduction. Lactic acid, a metabolic byproduct of glycolysis, is potentially toxic as it lowers the pH inside the parasite. Plasmodium falciparum formate-nitrite transporter (PfFNT), a 34-kDa transmembrane protein, has been identified as a novel drug target as it exports lactate from inside the parasite to the surrounding parasitophorous vacuole within the erythrocyte cytosol. The structure and detailed molecular mechanism of this membrane protein are not yet available. Here we present structures of PfFNT in the absence and presence of the functional inhibitor MMV007839 at resolutions of 2.56 Å and 2.78 Å using single-particle cryo-electron microscopy. Genetic analysis and transport assay indicate that PfFNT is able to transfer lactate across the membrane. Combined, our data suggest a stepwise displacement mechanism for substrate transport. The PfFNT membrane protein is capable of picking up lactate ions from the parasite's cytosol, converting them to lactic acids and then exporting these acids into the extracellular space.
History
DepositionMay 19, 2021-
Header (metadata) releaseDec 8, 2021-
Map releaseDec 8, 2021-
UpdateJun 4, 2025-
Current statusJun 4, 2025Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.8
  • Imaged by UCSF Chimera
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  • Surface view colored by cylindrical radius
  • Surface level: 0.8
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-7mxy
  • Surface level: 0.8
  • Imaged by UCSF Chimera
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  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-7mxy
  • Imaged by Jmol
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_24076.png

Downloads & links

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Map

FileDownload / File: emd_24076.map.gz / Format: CCP4 / Size: 3.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesX (Sec.)Y (Row.)Z (Col.)
1.07 Å/pix.
x 87 pix.
= 93.09 Å		1.07 Å/pix.
x 104 pix.
= 111.28 Å		1.07 Å/pix.
x 102 pix.
= 109.14 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

generated in cubic-lattice coordinate

Voxel sizeX=Y=Z: 1.07 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.5 / Movie #1: 0.8
Minimum - Maximum-4.1614094 - 6.3179297
Average (Standard dev.)-0.000000000019406 (±0.43192542)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderZYX
Origin102101106
Dimensions10410287
Spacing87104102
CellA: 93.090004 Å / B: 111.28001 Å / C: 109.14001 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.071.071.07
M x/y/z87104102
origin x/y/z0.0000.0000.000
length x/y/z93.090111.280109.140
α/β/γ90.00090.00090.000
start NX/NY/NZ106102101
NX/NY/NZ87104102
MAP C/R/S321
start NC/NR/NS101102106
NC/NR/NS10210487
D min/max/mean-4.1616.318-0.000

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Supplemental data

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Additional map: #1

Fileemd_24076_additional_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : PfFNT-inhibitor complex

EntireName: PfFNT-inhibitor complex
Components
  • Complex: PfFNT-inhibitor complex
    • Protein or peptide: Formate-nitrite transporter
  • Ligand: (Z)-4,4,5,5,5-pentakis(fluoranyl)-1-(4-methoxy-2-oxidanyl-phenyl)-3-oxidanyl-pent-2-en-1-one
  • Ligand: water

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Supramolecule #1: PfFNT-inhibitor complex

SupramoleculeName: PfFNT-inhibitor complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Plasmodium falciparum 3D7 (eukaryote)

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Macromolecule #1: Formate-nitrite transporter

MacromoleculeName: Formate-nitrite transporter / type: protein_or_peptide / ID: 1 / Number of copies: 5 / Enantiomer: LEVO
Source (natural)Organism: Plasmodium falciparum (isolate 3D7) (eukaryote) / Strain: isolate 3D7
Molecular weightTheoretical: 34.492281 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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

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Macromolecule #2: (Z)-4,4,5,5,5-pentakis(fluoranyl)-1-(4-methoxy-2-oxidanyl-phenyl)...

MacromoleculeName: (Z)-4,4,5,5,5-pentakis(fluoranyl)-1-(4-methoxy-2-oxidanyl-phenyl)-3-oxidanyl-pent-2-en-1-one
type: ligand / ID: 2 / Number of copies: 5 / Formula: HV6
Molecular weightTheoretical: 312.189 Da
Chemical component information

ChemComp-HV6:
(Z)-4,4,5,5,5-pentakis(fluoranyl)-1-(4-methoxy-2-oxidanyl-phenyl)-3-oxidanyl-pent-2-en-1-one

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Macromolecule #3: water

MacromoleculeName: water / type: ligand / ID: 3 / Number of copies: 2 / Formula: HOH
Molecular weightTheoretical: 18.015 Da
Chemical component information

ChemComp-HOH:
WATER

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 38.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.18 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 1044196
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION

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