Plasmodium falciparum 26S proteasome (Pf26S) (Pf26S)

The Plasmodium falciparum 26S proteasome is a large, multi-subunit enzyme complex that serves as the primary machinery for regulated protein degradation within the malaria parasite (Li et al., 2016). It is composed of a 20S catalytic core particle and 19S regulatory particles, which together maintain cellular proteostasis by degrading misfolded, damaged, or regulatory proteins tagged with ubiquitin (Kirkman et al., 2022). This proteasome is essential for the parasite's survival and rapid replication during the erythrocytic stage, as well as for its transition between different life cycle stages (UniProt, 2024). Because the parasite relies heavily on efficient protein turnover to support its high metabolic demands, the Pf26S proteasome has emerged as a high-priority therapeutic target (Kirkman et al., 2022). Inhibition of the catalytic subunits within the 20S core leads to a lethal accumulation of polyubiquitinated proteins, triggering proteotoxic stress and parasite death (Zhan et al., 2021). While human proteasome inhibitors are used in cancer therapy, current antimalarial drug development focuses on identifying compounds like LXE408 that selectively target the parasite's proteasome to minimize host toxicity and side effects such as neuropathy (Novartis, 2021).

Other names

Plasmodium falciparum 20S proteasomePf20SMalaria parasite proteasomePf26S proteasome

Inhibition of the catalytic activity of the 20S core particle subunits (beta-1, beta-2, or beta-5), leading to the disruption of protein homeostasis and induction of the unfolded protein response (Zhan et al., 2021; Kirkman et al., 2022).