Penicillin-binding protein transpeptidase (PBP transpeptidase)

Penicillin-binding protein transpeptidases (PBPs) are a family of essential bacterial enzymes responsible for the cross-linking of peptidoglycan chains, a critical step in the synthesis and maintenance of the bacterial cell wall[1][2][5]. They are the primary targets of β-lactam antibiotics (penicillins, cephalosporins, carbapenems, and monobactams)[2][3][5]. PBPs contain a C-terminal transpeptidase domain that catalyzes the formation of peptide cross-links between glycan chains, thereby providing structural integrity to the cell wall[1][2][4][5]. The inactivation of PBPs by covalent acylation of an active site serine by β-lactam antibiotics leads to inhibition of cell wall synthesis and bacterial cell death. PBPs are a heterogeneous family, categorized mainly as high-molecular-weight (HMW) and low-molecular-weight (LMW) PBPs, with subclass variations depending on domain organization, function, and bacterial species[1][2][4][5]. Mutations or acquisition of alternative PBPs, such as PBP2a in methicillin-resistant *Staphylococcus aureus* (MRSA), underlie important mechanisms of antibiotic resistance. PBPs are not found in eukaryotes, making them highly selective drug targets[7]. Note: The term “Penicillin-binding protein transpeptidase” is a class rather than a unique molecule, encompassing various paralogs (e.g., PBP2, PBP3) with conserved enzymatic functions but different bacterial localizations and specificities[2][3][4][5].

Other names

Penicillin-binding protein (PBP)PBP transpeptidase domainTranspeptidase domain of penicillin-binding proteinPBP2 (specific paralogs such as PBP2a, PBP2b, PBP3, etc., in different bacteria)

β-lactam antibiotics mimic the D-Ala-D-Ala moiety of peptidoglycan precursors and bind covalently to the active site serine of the transpeptidase, irreversibly inactivating the enzyme and blocking cross-linking of the bacterial cell wall[1][2][3][5].