Evidence map›Paper›PMID 33471955›Full record

ArticleEMBO reports2021

Structural basis of transport and inhibition of the Plasmodium falciparum transporter PfFNT.

Meinan Lyu, Chih-Chia Su, James W Kazura, Edward W Yu

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.7field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Structural analysis of resistance-nodulation cell division transporters.Microbiology and molecular biology reviews : MMBR · 2024
    Review
  5. Article
  6. Review
  7. Review
  8. Frontiers in cellular and infection microbiology · 2022
    Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Meinan LyuDepartment of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.ORCID 0000-0001-5795-0232
Chih-Chia SuDepartment of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
James W KazuraCenter for Global Health & Diseases, Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.ORCID 0000-0002-6390-634X
Edward W YuDepartment of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.ORCID 0000-0001-5912-1227
University School · USCenter for Global Health · US

Funding

Vector Biology of Invasive Anopheles stephensi in Rural to Urban Landscapes in EthiopiaU19AI129326 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI Guiyun Yan · 2017 to 2026
$19.9M
Emerging antibiotic resistance in Gram-negative pathogensR01AI145069 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI YU, EDWARD W · 2019 to 2023
$3.3M
Kruppel-Like Factor 2 Counters Vascular and Immunologic Dysfunction in Child Cerebral MalariaR01AI130131 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI KAZURA, JAMES WALTER · 2017 to 2021
$3.0M
NIAID NIH HHS R01 AI130131NIAID NIH HHS R01 AI145069NIAID NIH HHS U19 AI129326NIH HHS R01AI130131NIH HHS R01AI145069NIH HHS U19AI129326
6 · The paper itself

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 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.

Indexed as

NitritesPlasmodium falciparumCryoelectron MicroscopyFormatesProtozoan ProteinsFormatesNitritesProtozoan Proteinscryo-EMMalariamembrane proteinPfFNTPlasmodium falciparum transporter

Identifiers

PMID33471955
PMCPMC7926216
OpenAlexW3123314875

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.