Helicobacter pylori urease and Helicobacter pylori cysteine-rich protein family (Urease: H. pylori urease (HPU); Cysteine-rich proteins: Hcp family)

Helicobacter pylori urease is a nickel-dependent metalloenzyme critical for bacterial survival in the gastric mucosa, catalyzing the hydrolysis of urea to ammonia and CO₂, which neutralizes gastric acid and enables colonization. Urease is a large oligomeric enzyme composed of α and β subunits (UreA and UreB) arranged into a dodecameric assembly, with a highly conserved active site containing two nickel ions[1][3][9]. Activation and maturation require accessory proteins (UreD, UreF, UreG, and UreE)[3][5]. Urease is a well-validated therapeutic target for antibiotics and specific enzyme inhibitors[1]. Helicobacter cysteine-rich proteins (Hcps) are a family of secreted, disulfide-rich proteins unique to Helicobacter and Campylobacter genera, with roles in immune modulation, monocyte-to-macrophage differentiation, and are recognized by the host immune system[2][4]. There is ongoing research into their biological roles, but some (e.g., HcpA) directly modulate human immune cells, and their sequence features (multiple cysteine motifs and Sel1-repeats) suggest a role in host–pathogen interaction[2][4][6][8]. Hcps may contribute to inflammation and possibly to cancer progression in infected tissues[2][4].

Other names

UreA/BNickel-dependent ureaseHPUHcp family (HcpA, HcpB, HcpC, HcpD, HcpE, HP0211, HP1098, HP0160, HP0235, etc.)Helicobacter cysteine-rich protein

Urease inhibitors: Block active site by chelating nickel or binding urease active-site flap, preventing urea hydrolysis and ammonia formation. Disrupt bacterial acid resistance leading to bacterial eradication under acidic gastric conditions. Hcp proteins: No direct drugs, but potential mechanisms include inhibition of protein expression, neutralizing antibodies, or interference with protein–protein interactions to reduce immunomodulatory effects.