Peptidoglycan D,D-transpeptidase (Penicillin-binding protein) (PBP)

Peptidoglycan D,D-transpeptidase, widely known as Penicillin-binding protein (PBP), is an essential enzyme in Escherichia coli that catalyzes the final cross-linking step of peptidoglycan biosynthesis (UniProt P0AD68, P02918). This process involves the formation of a peptide bond between the penultimate D-alanine of one peptidoglycan strand and the meso-diaminopimelic acid of an adjacent strand, which is vital for maintaining the structural integrity of the bacterial cell wall (PMID: 18218610). In E. coli, specific isoforms such as PBP1a, PBP1b, PBP2, and PBP3 perform distinct roles in cell elongation, shape maintenance, and septation during cell division (UniProt P0AD68). These enzymes are the primary targets for beta-lactam antibiotics, including penicillins and cephalosporins, which mimic the D-alanyl-D-alanine substrate to covalently inhibit the enzyme's active site (StatPearls: Beta Lactam Antibiotics). Inhibition leads to a weakened cell wall, osmotic instability, and subsequent bacterial cell death (PMID: 18218610). Consequently, PBPs are central to the treatment of various E. coli-mediated infections, although their efficacy is increasingly challenged by the emergence of modified PBPs and beta-lactamase enzymes.

Other names

Penicillin-binding proteinD,D-transpeptidaseMurein transpeptidasePBP1aPBP1bPBP2PBP3FtsIMrdAMrcAMrcB

Covalent inhibition of the transpeptidase active site by acting as a structural analog of the D-alanyl-D-alanine substrate, preventing peptidoglycan cross-linking.