Penicillin-binding protein of Helicobacter pylori (PBP)

Penicillin-binding proteins (PBPs) in Helicobacter pylori are essential enzymes responsible for the final stages of peptidoglycan biosynthesis, which is vital for maintaining the structural integrity and shape of the bacterial cell wall (UniProt, 2023). These proteins, including PBP1A, PBP2, and PBP3, catalyze the cross-linking of peptidoglycan strands via transpeptidation and carboxypeptidation reactions (NCBI, 2021). In the clinical management of H. pylori infections—which are strongly associated with chronic gastritis, peptic ulcers, and gastric cancer—PBPs serve as the primary targets for beta-lactam antibiotics such as amoxicillin (PubMed, PMID: 26163558). Amoxicillin acts as a structural analog of the D-alanyl-D-alanine terminus of peptidoglycan precursors, binding irreversibly to the PBP active site and preventing cell wall completion, which results in osmotic lysis of the bacterium (StatPearls, 2023). A major therapeutic challenge is the emergence of amoxicillin resistance, often driven by specific point mutations in the pbp1A gene that decrease the binding affinity of the antibiotic to the enzyme (Journal of Antimicrobial Chemotherapy, 2020).

Other names

DD-transpeptidaseDD-carboxypeptidaseDD-endopeptidaseMurein transpeptidasePBP1APBP2PBP3

Inhibition of the transpeptidation reaction in peptidoglycan synthesis by covalently binding to the active site serine, leading to cell wall instability and bacterial lysis.