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Artemisinin-resistant Plasmodium falciparum Kelch13 mutant proteins display reduced heme-binding affinity and decreased artemisinin activation.

Communications biology - 13 Nov 2024

Rahman Abdur, Tamseel Sabahat, Dutta Smritikana, Khan Nawaal, Faaiz Mohammad, Rastogi Harshita, Nath Jyoti Rani, Haldar Kasturi, Chowdhury Pramit, Ashish, Bhattacharjee Souvik

Abstract excerpt

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...

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Identifiers

PMID: 39538019
DOI: 10.1038/s42003-024-07178-2
PMCID: PMC11561146

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