Penicillin-binding proteins 1A, 1B, 3, and 4 (Escherichia coli) (PBPs (1A, 1B, 3, 4))

Penicillin-binding proteins (PBPs) 1A, 1B, 3, and 4 are essential enzymes in Escherichia coli that catalyze the final stages of peptidoglycan biosynthesis, which is critical for maintaining the structural integrity and shape of the bacterial cell wall [1, 2, 5]. PBP1A (mrcA) and PBP1B (mrcB) are high-molecular-weight Class A bifunctional enzymes possessing both transglycosylase and transpeptidase activities; they are functionally redundant, but the presence of at least one is required for cell viability [3, 9]. PBP3 (ftsI) is a Class B transpeptidase specifically required for the formation of the division septum, and its inhibition leads to the arrest of cell division and the formation of long filaments [10, 12]. PBP4 (dacB) is a low-molecular-weight Class C enzyme with DD-carboxypeptidase and endopeptidase activities involved in the remodeling and maturation of the peptidoglycan layer [1, 9]. These proteins are the primary therapeutic targets for beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems, which act as suicide inhibitors by covalently binding to the active site serine [5, 8, 10]. Inhibition of these PBPs disrupts cell wall assembly, leading to osmotic instability, cell lysis, and bacterial death [4, 10].

Other names

mrcA (PBP1A)ponA (PBP1A)mrcB (PBP1B)ponB (PBP1B)ftsI (PBP3)pbpB (PBP3)dacB (PBP4)DD-transpeptidaseDD-carboxypeptidasePeptidoglycan glycosyltransferase

Covalent inhibition of the transpeptidase domain by acting as a structural analog of the D-alanyl-D-alanine terminus of peptidoglycan precursors, thereby preventing cell wall cross-linking and leading to bacterial lysis [2, 5, 8, 10].