{
      "number": 1,
      "eprintid": 3331,
      "date": "2024-11",
      "userid": 2,
      "rev_number": 3,
      "creators": [
        {
          "name": {
            "lineage": null,
            "given": "Abdur",
            "honourific": null,
            "family": "Rahman"
          }
        },
        {
          "name": {
            "lineage": null,
            "given": "Sabahat",
            "honourific": null,
            "family": "Tamseel"
          }
        },
        {
          "name": {
            "lineage": null,
            "given": "Smritikana",
            "honourific": null,
            "family": "Dutta"
          }
        },
        {
          "name": {
            "lineage": null,
            "given": "Nawaal",
            "honourific": null,
            "family": "Khan"
          }
        },
        {
          "name": {
            "lineage": null,
            "given": "Mohammad",
            "honourific": null,
            "family": "Faaiz"
          }
        },
        {
          "name": {
            "lineage": null,
            "given": "Harshita",
            "honourific": null,
            "family": "Rastogi"
          }
        },
        {
          "name": {
            "lineage": null,
            "given": "Jyoti Rani",
            "honourific": null,
            "family": "Nath"
          }
        },
        {
          "name": {
            "lineage": null,
            "given": "Kasturi",
            "honourific": null,
            "family": "Haldar"
          }
        },
        {
          "name": {
            "lineage": null,
            "given": "Pramit",
            "honourific": null,
            "family": "Chowdhury"
          }
        },
        {
          "name": {
            "lineage": null,
            "given": null,
            "honourific": null,
            "family": "Ashish"
          }
        },
        {
          "name": {
            "lineage": null,
            "given": "Souvik",
            "honourific": null,
            "family": "Bhattacharjee"
          }
        }
      ],
      "dir": "disk0\/00\/00\/33\/31",
      "lastmod": "2026-02-07 04:55:53",
      "pagerange": 1499,
      "publisher": "Springer Science and Business Media LLC",
      "metadata_visibility": "show",
      "eprint_status": "archive",
      "status_changed": "2026-02-07 04:55:53",
      "volume": 7,
      "datestamp": "2026-02-07 04:55:53",
      "uri": "http:\/\/crdd.osdd.net\/open\/id\/eprint\/3331",
      "type": "article",
      "title": "Artemisinin-resistant Plasmodium falciparum Kelch13 mutant proteins display reduced heme-binding affinity and decreased artemisinin activation",
      "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.",
      "publication": "Commun. Biol."
    }