Histidine-rich nickel-binding protein (Hpn) (Hpn)

Histidine-rich nickel-binding protein (Hpn) is a small, cytoplasmic protein (approximately 7 kDa) found in Helicobacter pylori that is essential for managing intracellular nickel concentrations. With a sequence comprising nearly 50% histidine residues, Hpn functions as a high-capacity nickel reservoir and a detoxification agent, protecting the bacterium from metal toxicity while ensuring a supply of nickel for vital enzymes like urease and hydrogenase (UniProt P0A0V2; PMID: 18463351). Urease activity is particularly crucial for H. pylori as it neutralizes stomach acid, allowing the pathogen to colonize the gastric mucosa and cause diseases such as gastritis and peptic ulcers (PMID: 21853345). Hpn is a significant therapeutic target because it is unique to the Helicobacter genus and lacks a human ortholog. Bismuth-based drugs, which are standard components of H. pylori eradication therapies, exert their antibacterial effects in part by binding to Hpn with higher affinity than nickel, thereby disrupting the protein's ability to maintain nickel homeostasis (PMID: 21462068). Targeting Hpn offers a strategy to inhibit the survival mechanisms of H. pylori, potentially overcoming issues related to conventional antibiotic resistance.

Other names

Nickel-binding protein HpnHistidine-rich proteinHP0616

Bismuth ions competitively bind to the histidine-rich regions of Hpn, displacing nickel ions and disrupting nickel homeostasis, which subsequently inhibits the activity of essential nickel-dependent enzymes like urease.