Penicillin-binding protein 1c (PBP1c) (PBP1c)

Penicillin-binding protein 1c (PBP1c), encoded by the mrcC gene in Escherichia coli, is a Class A high-molecular-weight penicillin-binding protein (UniProt P0AD68). It is a bifunctional enzyme containing both a transglycosylase domain, responsible for the polymerization of the glycan strands of peptidoglycan, and a transpeptidase domain, which catalyzes the cross-linking of peptide side chains (Schiffer & Holtje, 1999). Although PBP1c is not essential for bacterial viability under standard laboratory conditions, it contributes to the robustness of the cell wall and can compensate for the loss of other PBPs like PBP1a or PBP1b (Sauvage et al., 2008). The transglycosylase domain is specifically inhibited by the antibiotic moenomycin, which prevents the formation of the carbohydrate backbone of the cell wall (van Heijenoort, 2001). While most beta-lactam antibiotics target the transpeptidase domain of PBPs, PBP1c generally exhibits lower affinity for these drugs compared to its counterparts (Macheboeuf et al., 2006). Consequently, PBP1c represents a secondary therapeutic target in the development of novel antibacterials aimed at disrupting bacterial cell wall assembly and overcoming resistance mechanisms.

Other names

PBP-1cmrcCponCPenicillin-binding protein 1CBifunctional penicillin-binding protein 1C

The transglycosylase domain of PBP1c catalyzes the transfer of the phospho-disaccharide-pentapeptide moiety from lipid II to the growing peptidoglycan chain. Inhibition of this domain, for example by moenomycin, prevents glycan chain elongation, leading to a compromised bacterial cell wall and eventual cell death (van Heijenoort, 2001; Schiffer & Holtje, 1999).