Penicillin-binding protein (Helicobacter pylori) (PBP)

Penicillin-binding proteins (PBPs) in Helicobacter pylori are a group of essential enzymes responsible for the assembly and maintenance of the bacterial peptidoglycan cell wall. These proteins, particularly PBP1A, PBP2, and PBP3, catalyze the transglycosylation and transpeptidation reactions that crosslink glycan strands, providing the cell with structural rigidity and protection against osmotic stress (UniProt). H. pylori infection is a primary cause of chronic gastritis and peptic ulcer disease, and it is strongly linked to the development of gastric adenocarcinoma (StatPearls: NBK544250). PBPs are the primary molecular targets for beta-lactam antibiotics, such as amoxicillin, which is a cornerstone of H. pylori eradication therapy (PubMed: 31422111). The drugs act by covalently binding to the PBP active site, mimicking the natural D-Ala-D-Ala substrate and irreversibly inhibiting the enzyme's crosslinking activity. However, the emergence of resistance, primarily through point mutations in the pbp1A gene that reduce drug binding affinity, poses a significant challenge to successful clinical treatment (PubMed: 25605355).

Other names

PBP1APBP2PBP3MrcAMrdAFtsIPeptidoglycan D-amino acid transpeptidaseD-alanyl-D-alanine carboxypeptidasePenicillin-binding protein 1APenicillin-binding protein 2Penicillin-binding protein 3

Beta-lactam antibiotics function as structural analogs of the D-alanyl-D-alanine terminus of peptidoglycan precursors. They bind covalently to the active-site serine residue of Penicillin-binding proteins (PBPs), specifically the transpeptidase domain. This irreversible inhibition prevents the cross-linking of peptidoglycan chains, which is essential for cell wall stability and integrity, eventually leading to bacterial cell lysis due to osmotic pressure.