Helicobacter pylori penicillin-binding protein (PBP) (PBP)

Helicobacter pylori penicillin-binding proteins (PBPs) are essential membrane-associated enzymes responsible for the final stages of peptidoglycan assembly in the bacterial cell wall. These proteins, including high-molecular-weight variants like PBP1, PBP2, and PBP3, possess transpeptidase and glycosyltransferase activities that facilitate the cross-linking of peptide side chains, ensuring the structural integrity and shape of the bacterium (UniProt P56068). In clinical practice, PBPs are the primary targets for beta-lactam antibiotics, such as amoxicillin, which covalently bind to the enzyme's active site to inhibit cell wall synthesis and trigger bacterial lysis (PubMed PMID: 11114253). H. pylori infections are a major cause of chronic gastritis, peptic ulcers, and gastric adenocarcinoma, making PBPs critical therapeutic targets for eradication (StatPearls NBK544250). However, the increasing prevalence of amoxicillin resistance, often driven by specific point mutations in the pbp1 gene that reduce antibiotic binding affinity, presents a significant challenge to standard treatment regimens (PubMed PMID: 26163558). Consequently, monitoring PBP mutations and developing novel inhibitors remain vital areas of research in managing H. pylori-related diseases.

Other names

PBP1PBP2PBP3Penicillin-binding protein 1Penicillin-binding protein 2Penicillin-binding protein 3Peptidoglycan synthaseTranspeptidaseD-alanyl-D-alanine carboxypeptidase

Beta-lactam antibiotics act as structural analogs of the D-Ala-D-Ala terminus of peptidoglycan precursors, covalently binding to the active site of penicillin-binding proteins (PBPs) to inhibit the transpeptidation reaction, thereby preventing cell wall cross-linking and leading to bacterial cell death.