Urease accessory protein G (UreG) (UreG)

Urease accessory protein G (UreG) is a small GTPase and metallochaperone that plays a vital role in the maturation of urease, a nickel-dependent enzyme found in various bacteria, fungi, and plants [1, 7]. It functions by coupling the energy from GTP hydrolysis to the insertion of nickel ions into the apo-urease active site, a process requiring a complex assembly with other accessory proteins such as UreD (or UreH), UreF, and UreE [10, 12]. In pathogenic bacteria like Helicobacter pylori, urease activity is essential for survival in the acidic environment of the human stomach, as it produces ammonia to neutralize gastric acid [1, 12]. This colonization leads to significant clinical conditions, including chronic gastritis, peptic ulcers, and an increased risk of gastric cancer [1, 6]. UreG has emerged as a novel therapeutic target for antimicrobial development because direct inhibition of the urease enzyme is often hindered by its deeply buried active site and high substrate specificity [1, 6]. Clinically used bismuth-based drugs, such as colloidal bismuth subcitrate, have been shown to exert their effects by binding to UreG and inhibiting its GTPase activity, thereby preventing the formation of functional urease [1, 2]. Targeting UreG offers a strategic advantage in overcoming antibiotic resistance and improving the efficacy of treatments for urease-associated infections in both the gastrointestinal and urinary tracts [4, 6].

Other names

Urease accessory protein UreGNi-binding GTPaseMetallochaperone UreGUrease maturation protein UreG

Inhibition of GTPase activity, disruption of urease maturation, and prevention of nickel insertion into the urease active site.