ATP-dependent Clp protease ATP-binding subunit ClpX (Helicobacter pylori) (ClpX)

ATP-dependent Clp protease ATP-binding subunit ClpX (ClpX) is a vital molecular chaperone and ATPase in Helicobacter pylori that belongs to the AAA+ (ATPases Associated with diverse cellular Activities) family (UniProt P56001). It functions by recognizing, unfolding, and translocating specific protein substrates into the ClpP protease chamber for degradation, thereby maintaining bacterial proteostasis and supporting survival under stress (Sun et al., Chem. Sci., 2015). In the context of H. pylori treatment, ClpX has been identified as a primary molecular target for bismuth-based drugs, such as bismuth subcitrate potassium. Bismuth ions (Bi3+) exert their antibacterial effect by binding to the highly conserved zinc-binding domain of ClpX, displacing the essential zinc ion and triggering the irreversible disassembly of the active hexameric enzyme (Yuan et al., Metallomics, 2020). This inhibition disrupts the bacterial protein quality control system, contributing to the eradication of the pathogen in patients with peptic ulcers or chronic gastritis (Wang et al., J. Inorg. Biochem., 2018).

Other names

ClpX chaperoneATP-dependent Clp protease subunit ClpXH. pylori ClpXAAA+ ATPase ClpX

Bismuth ions (Bi3+) bind to the highly conserved N-terminal zinc-binding domain (ZBD) of ClpX, displacing the native zinc ion (Zn2+). This displacement causes the irreversible disassembly of the functional hexameric ClpX complex, thereby inhibiting its ATPase and chaperone activities and disrupting bacterial protein homeostasis (Sun et al., Chem. Sci., 2015; Yuan et al., Metallomics, 2020).