Penicillin-binding protein 5 (Enterococcus faecalis) (PBP5)

Penicillin-binding protein 5 (PBP5) is a membrane-associated enzyme in Enterococcus faecalis that plays a critical role in the final stages of bacterial cell wall synthesis (UniProt: P0A2B5). It functions as a transpeptidase, catalyzing the cross-linking of peptidoglycan chains which provides structural integrity to the bacterium (PubMed: 16109930). PBP5 is classified as a low-affinity penicillin-binding protein, meaning it can continue to function even in the presence of concentrations of beta-lactam antibiotics that inhibit other PBPs (PubMed: 21628498). This characteristic is a primary driver of intrinsic resistance to cephalosporins and contributes to reduced susceptibility to penicillins in enterococci. While E. faecalis is typically more susceptible to ampicillin than E. faecium, the overproduction or mutational alteration of PBP5 can lead to clinical resistance and treatment challenges (PubMed: 11959166). Drugs targeting this protein, such as ampicillin, work by forming a stable acyl-enzyme intermediate that halts cell wall assembly, leading to bacterial cell death (PubMed: 10449071).

Other names

D-alanyl-D-alanine carboxypeptidasePeptidoglycan D-amino acid transpeptidasePBP-5pbpZPBP 5

Covalent binding to the active site serine residue, inhibiting the transpeptidase activity required for peptidoglycan cross-linking.