Characterization and Inhibition of the Chaperone Function of Plasmodium falciparum Glucose-Regulated Protein 94 kDa (PfGrp94).

Plasmodium falciparum expresses four heat shock protein 90 (Hsp90) members. Among these, one, glucose-regulated protein 94 (PfGrp94), is localized in the endoplasmic reticulum (ER). Both the cytosolic and ER-based Hsp90s are essential for parasite survival under all growth conditions.

screening of selective ATP mimicking inhibitors targeting the Grp94.

parasites export more than 400 proteins to remodel the host cell environment and increase its chances of surviving and reproducing. The endoplasmic reticulum (ER) plays a central role in protein export by facilitating protein sorting and folding. The ER resident member of the Hsp90 family, glucose-regulated protein 94 (Grp94), is a molecular chaperone that facilitates the proper folding of client proteins in the ER lumen.