Penicillin-binding proteins 3, 1a, and 1b (PBP3, PBP1a, PBP1b)

Penicillin-binding proteins (PBPs) are a group of essential bacterial enzymes involved in the final stages of peptidoglycan biosynthesis, which is the primary component of the bacterial cell wall. PBP1a and PBP1b are high-molecular-weight bifunctional enzymes that possess both transglycosylase activity for glycan chain elongation and transpeptidase activity for peptide cross-linking. PBP3, often referred to as FtsI in Gram-negative bacteria, is a specialized transpeptidase essential for the formation of the division septum during binary fission. Because these proteins are located on the outer face of the cytoplasmic membrane and are unique to bacteria, they serve as the primary therapeutic targets for beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems. Inhibition of these PBPs disrupts cell wall integrity and cell division, triggering autolytic enzymes that lead to bacterial death. Mutations in the genes encoding these PBPs, particularly PBP3, are a significant mechanism of clinical resistance in pathogens such as Pseudomonas aeruginosa and Haemophilus influenzae.

Other names

PBPsFtsI (PBP3)mrcA (PBP1a)mrcB (PBP1b)Peptidoglycan D-glutamyl-L-lysine transpeptidaseD-alanyl-D-alanine carboxypeptidaseTranspeptidaseTransglycosylase

Beta-lactam antibiotics act as structural analogs of the D-alanyl-D-alanine terminus of peptidoglycan precursors, covalently binding to the active site serine of Penicillin-binding proteins (PBPs). This irreversible inhibition prevents the transpeptidation reaction required for cross-linking peptidoglycan chains, leading to a weakened cell wall, osmotic instability, and eventual bacterial cell lysis.