Investigation of a cryptic ligand binding site on Plasmodium falciparum Hsp90.

ABSTRACT: The molecular chaperone heat shock protein 90 (Hsp90) has an important role in maintaining proteostasis in Plasmodium parasites, the causative agents of malaria, and is of interest as a potential antimalarial drug target. Inhibitors targeting its well-characterized N-terminal ATP-binding site are lethal, but the development of high-affinity binders with selectivity for the Plasmodium over the human homolog has been challenging given the high conservation of this domain. A binding site in the less conserved Hsp90 C-terminus has been reported to interact with nucleotides and inhibitors in other eukaryotic systems, which could offer an alternative route for antimalarial design. Herein, we characterize the potential ligandability of the C-terminus in the Plasmodium falciparum chaperone PfHsp90

SUBMITTER: Mansfield CR 

PROVIDER: S-EPMC12411742 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature