ArticleCommunications biology2024
Artemisinin-resistant Plasmodium falciparum Kelch13 mutant proteins display reduced heme-binding affinity and decreased artemisinin activation.
Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled 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.
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
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Phytochemical synergy in artemisia annua herbal tea against malaria: a systematic review of its efficacy and safety in the context of emerging Pfkelch13 resistance.Infectious diseases of poverty · 2026Pooled it
- Antiplasmodial Compounds fromInternational journal of molecular sciences · 2026Article
- Emergence and spread of Plasmodium falciparum PX1 polymorphisms associated with decreased susceptibility to antimalarials in Uganda.Nature medicine · 2026Article
- Covalent Inhibitors in Antimicrobial Drug Development-Beyond β-Lactams.Molecules (Basel, Switzerland) · 2026Review
- Why are iron chelators not as effective as artemisinin in killing malaria parasites?Parasites & vectors · 2026Article
- Global-scale population genetic analysis of Plasmodium falciparum identifies region-specific patterns of malaria parasite adaptation.Nature communications · 2026Article
- PfPI3K inhibition reversed artemisinin resistance by increasing ROS and ubiquitinated protein levels in Plasmodium falciparum.Communications biology · 2025Article
- Role of novel mutations in food vacuole transporters beyond K13-mediated artemisinin resistance inAntimicrobial agents and chemotherapy · 2025Article
- Vesicular mechanisms of drug resistance in apicomplexan parasites.Microbiology and molecular biology reviews : MMBR · 2025Review
- Antiplasmodial Screening of Phikud Navakot Formulation and In Vivo Evaluation, Toxicity, and Phytochemical Profiling of the PotentScientifica · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
The potency of frontline antimalarial drug artemisinin (ART) derivatives is triggered by heme-induced cleavage of the endoperoxide bond to form reactive heme-ART alkoxy radicals and covalent heme-ART adducts, which are highly toxic to the parasite. ART-resistant (ART-R) parasites with mutations in the Plasmodium falciparum Kelch-containing protein Kelch13 (PfKekch13) exhibit impaired hemoglobin uptake, reduced yield of hemoglobin-derived heme, and thus decreased ART activation. However, any direct involvement of PfKelch13 in heme-mediated ART activation has not been reported. Here, we show that the purified recombinant PfKelch13 wild-type (WT) protein displays measurable binding affinity for iron and heme, the main effectors for ART activation. The heme-binding property is also exhibited by the native PfKelch13 protein from parasite culture. The two ART-R recombinant PfKelch13 mutants (C580Y and R539T) display weaker heme binding affinities compared to the ART-sensitive WT and A578S mutant proteins, which further translates into reduced yield of heme-ART derivatives when ART is incubated with the heme molecules bound to the mutant PfKelch13 proteins. In conclusion, this study provides the first evidence for ART activation via the heme-binding propensity of PfKelch13. This mechanism may contribute to the modulation of ART-R levels in malaria parasites through a novel function of PfKelch13.
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.