Penicillin-binding protein 1A of Helicobacter pylori (PBP1A)

Penicillin-binding proteins (PBPs) are a family of enzymes crucial for the synthesis and remodeling of bacterial peptidoglycan, which determines cell wall structure and shape. In *Helicobacter pylori*, several PBPs are encoded in the genome, with PBP1A being a prominent member involved in both transglycosylation and transpeptidation activities required for peptidoglycan biosynthesis[9][4]. PBPs are named for their ability to bind penicillin and related beta-lactam antibiotics, which inhibit their enzymatic activity and thus disrupt cell wall formation, ultimately causing bacterial lysis. *H. pylori* PBPs are central to bacterial survival in the acidic environment of the stomach, enabling the bacterium’s helical shape and colonization[2][3][10]. Amoxicillin and other beta-lactam antibiotics exert their antibacterial effect by binding to the active site of PBPs, specifically the serine residue, and inhibiting peptidoglycan cross-linking[9][7]. Resistance to amoxicillin has been associated with specific point mutations in pbp1a, which alter drug-binding domains or access tunnels, making drug binding less effective[9]. These proteins are therefore important therapeutic targets in the treatment of *H. pylori*-associated pathologies, and monitoring pbp1a mutations serves as a biomarker for anticipating treatment outcomes[9]. PBPs in *H. pylori* are structurally and functionally distinct; for example, HcpB is a unique cysteine-rich penicillin-binding protein from H. pylori that displays a novel fold distinct from other known PBPs, underscoring the diversity within this family[1]. The safety concern for targeting PBPs primarily relates to the development of antibiotic resistance and disruption of beneficial microbiota due to broad-spectrum antibiotic use.

Other names

Penicillin-binding protein 1APBP1APBPs (class includes PBP1, PBP2, PBP3, PBP4)Penicillin-binding proteins

Beta-lactams inhibit PBPs by covalently binding their active site serine residue, preventing peptidoglycan cross-linking and cell wall synthesis, leading to bacterial cell death