Penicillin-binding protein 3 and Penicillin-binding protein 1b (PBP3 and PBP1b)

Penicillin-binding proteins (PBPs) are essential enzymes located in the bacterial periplasm of Gram-negative bacteria, where they catalyze the final stages of peptidoglycan cell wall assembly (Sauvage et al., 2008). Penicillin-binding protein 3 (PBP3, also known as FtsI) is a class B PBP that functions as a monofunctional transpeptidase specifically required for septum formation during cell division (UniProt P0AD68; Wikipedia). Penicillin-binding protein 1b (PBP1b, also known as PonA or MrcB) is a class A PBP that possesses bifunctional glycosyltransferase and transpeptidase activities, contributing to both cell wall synthesis and repair (UniProt P02919; NIH). These proteins are the primary targets of beta-lactam antibiotics, which covalently bind to the active site serine, inhibiting the cross-linking of peptidoglycan strands. This inhibition compromises the structural integrity of the bacterial cell wall, leading to cell filamentation (in the case of PBP3 inhibition), lysis, and death (StatPearls). Resistance to drugs targeting these PBPs is a major clinical challenge, often mediated by the production of beta-lactamases or mutations in the PBP genes that reduce drug affinity (PubMed).

Other names

FtsIPonAMrcBSeptum formation protein IBifunctional transglycosylase-transpeptidase PBP1bPBP-3PBP-1b

Covalent inhibition of the transpeptidase domain via acylation of the catalytic serine residue, which mimics the D-alanyl-D-alanine substrate and prevents the cross-linking of peptidoglycan chains, leading to cell wall lysis (Sauvage et al., 2008; NIH).