Plasmodium falciparum cysteine proteases and translationally controlled tumor protein homolog (Falcipains/PfTCTP)

Plasmodium cysteine proteases and the translationally controlled tumor protein (TCTP) homolog are critical components in the pathogenesis of malaria, specifically caused by Plasmodium falciparum. The cysteine proteases, primarily Falcipain-2 and Falcipain-3, are localized in the parasite's food vacuole where they catalyze the degradation of host hemoglobin, a process essential for providing amino acids to the growing parasite [1]. The TCTP homolog is a multifunctional protein involved in cell cycle regulation and calcium homeostasis, and it has been identified as a specific binding target for artemisinin [2]. Artemisinin and its derivatives (ACTs) are the cornerstone of modern malaria treatment; they are believed to exert their effect by being activated by heme-derived iron, subsequently inhibiting falcipain activity and covalently alkylating TCTP [3]. This dual-targeting mechanism leads to the disruption of metabolic and regulatory pathways, resulting in rapid parasite clearance. However, the emergence of resistance linked to mutations in the Kelch13 protein represents a significant threat to the efficacy of drugs targeting these pathways [4]. References: [1] Somsak et al. (2011) PMID: 21458530; [2] Bhisutthibhan et al. (1998) PMID: 9733625; [3] Wang et al. (2015) PMID: 26605430; [4] Ariey et al. (2014) PMID: 24352242.

Other names

Falcipain-2Falcipain-3PfTCTPHistamine-releasing factor homologHRFTCTP

Inhibition of hemoglobin degradation via falcipain blockade and covalent alkylation of the TCTP protein