ArticleNature communications2023
pH-dependence of the Plasmodium falciparum chloroquine resistance transporter is linked to the transport cycle.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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.
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.
Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- Article
- Collateral hypersensitivity between ZY19489 and piperaquine neutralizes PfCRT-mediated drug efflux and Plasmodium falciparum resistance.Nature communications · 2026Article
- Understanding, inhibiting, and engineering membrane transporters with high-throughput mutational screens.Cell chemical biology · 2025Review
- Combating Malaria: Targeting the Ubiquitin-Proteasome System to Conquer Drug Resistance.Tropical medicine and infectious disease · 2025Review
- Targeting Malaria's Achilles' Heels: A Review of Plasmodium Life Cycle Vulnerabilities for Drug Discovery.Current topics in medicinal chemistry · 2025Review
- VPS28 regulates triglyceride synthesis via ubiquitination in bovine mammary epithelial cells.Scientific reports · 2024Article
- pH-dependence of the Plasmodium falciparum chloroquine resistance transporter is linked to the transport cycle.Nature communications · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The chloroquine resistance transporter, PfCRT, of the human malaria parasite Plasmodium falciparum is sensitive to acidic pH. Consequently, PfCRT operates at 60% of its maximal drug transport activity at the pH of 5.2 of the digestive vacuole, a proteolytic organelle from which PfCRT expels drugs interfering with heme detoxification. Here we show by alanine-scanning mutagenesis that E207 is critical for pH sensing. The E207A mutation abrogates pH-sensitivity, while preserving drug substrate specificity. Substituting E207 with Asp or His, but not other amino acids, restores pH-sensitivity. Molecular dynamics simulations and kinetics analyses suggest an allosteric binding model in which PfCRT can accept both protons and chloroquine in a partial noncompetitive manner, with increased proton concentrations decreasing drug transport. Further simulations reveal that E207 relocates from a peripheral to an engaged location during the transport cycle, forming a salt bridge with residue K80. We propose that the ionized carboxyl group of E207 acts as a hydrogen acceptor, facilitating transport cycle progression, with pH sensing as a by-product.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.