Penicillin-binding protein 6 (PBP6) (PBP6)

Penicillin-binding protein 6 (PBP6) is a low-molecular-weight (LMW) enzyme primarily found in Gram-negative bacteria like Escherichia coli, where it is encoded by the dacC gene (UniProt P08506). It functions as a D-alanyl-D-alanine carboxypeptidase, responsible for removing the terminal D-alanine residue from the pentapeptide side chains of peptidoglycan precursors (PubMed: 16428397). This activity is crucial for regulating the degree of peptidoglycan cross-linking and maintaining the structural integrity and shape of the bacterial cell wall during growth (PubMed: 10411740). While PBP6 is often considered non-essential for bacterial viability under laboratory conditions, it plays a significant role in cell wall maturation and the overall fitness of the organism. As a member of the PBP family, it is a target for beta-lactam antibiotics, which mimic the D-Ala-D-Ala substrate and form a stable, covalent acyl-enzyme complex that inhibits the enzyme's function (PubChem). Understanding PBP6 is vital for addressing bacterial infections and the development of antimicrobial resistance, as its presence and activity can influence the efficacy of cell-wall-targeting drugs (PubMed: 21859938).

Other names

D-alanyl-D-alanine carboxypeptidasedacCLow-molecular-weight penicillin-binding protein 6PBP-6

Beta-lactam antibiotics act as substrate analogs that covalently bind to the active site serine of penicillin-binding proteins, inhibiting their carboxypeptidase or transpeptidase activity and leading to defective cell wall synthesis and bacterial lysis (PubMed: 16428397, PubChem).