Low-molecular-weight penicillin-binding protein (LMW PBP)

Low-molecular-weight penicillin-binding proteins (LMW PBPs) are a group of bacterial enzymes, primarily classified as Class C and Class D PBPs, that are essential for the maturation and remodeling of the peptidoglycan cell wall (Sauvage et al., 2008). Unlike high-molecular-weight PBPs that catalyze the polymerization of the glycan chain, LMW PBPs typically function as DD-carboxypeptidases or endopeptidases (Macheboeuf et al., 2006). They regulate the degree of peptidoglycan cross-linking by cleaving the terminal D-alanine from pentapeptide side chains, thereby influencing bacterial cell shape and division (Typas et al., 2011). These proteins are critical targets for beta-lactam antibiotics, which mimic the D-alanyl-D-alanine substrate and covalently bind to the active-site serine, leading to enzyme inactivation (Bush & Bradford, 2016). Although some LMW PBPs are non-essential for viability in certain laboratory conditions, they are vital for bacterial fitness, stress response, and pathogenesis during infection (Zapun et al., 2008). Inhibition of these targets contributes to the overall bactericidal effect of cell-wall-active agents by inducing structural instability and triggering autolytic pathways (Nelson & Young, 2000).

Other names

Class C penicillin-binding proteinClass D penicillin-binding proteinDD-carboxypeptidaseDD-endopeptidaseD-alanyl-D-alanine carboxypeptidasePBP4PBP5PBP6

Covalent inhibition of the active-site serine residue by acting as a structural analog of the D-alanyl-D-alanine substrate, thereby preventing DD-carboxypeptidase or endopeptidase activity and disrupting peptidoglycan maturation.