D,D-carboxypeptidase (DD-CPase)

Bacterial D,D-carboxypeptidases are essential enzymes involved in the final stages of peptidoglycan biosynthesis and cell wall remodeling in both Gram-positive and Gram-negative bacteria (UniProt, 2023). These enzymes, often classified as low-molecular-weight penicillin-binding proteins (LMW PBPs), catalyze the removal of the terminal D-alanine residue from the pentapeptide side chains of peptidoglycan precursors (PubMed: 16291668). By controlling the availability of these precursors, they regulate the extent of cross-linking within the bacterial cell wall, which is critical for maintaining osmotic stability and proper cell shape (Nature Reviews Microbiology, 2008). Because they possess a high affinity for beta-lactam antibiotics, they serve as significant targets for antimicrobial therapy. Drugs like penicillins and cephalosporins act as substrate analogs, covalently binding to the active site serine and inhibiting the enzyme's function (StatPearls, 2023). While not always the primary lethal target of beta-lactams, their inhibition contributes to cell wall defects and eventual bacterial lysis. Understanding these enzymes is vital for addressing antibiotic resistance, as modifications in these proteins can decrease drug efficacy.

Other names

D-alanyl-D-alanine carboxypeptidasePenicillin-binding protein 5PBP5Penicillin-binding protein 6PBP6Low-molecular-weight penicillin-binding proteinLMW PBPdacAdacBdacC

Inhibition of peptidoglycan cross-linking regulation by acting as a substrate analog that forms a stable, slowly-hydrolyzing acyl-enzyme intermediate with the active-site serine, preventing the removal of the terminal D-alanine from peptidoglycan precursors (StatPearls, 2023; PubMed: 16291668).