Penicillin-binding protein 4 (PBP4)

Penicillin-binding protein 4 (PBP4) is a low-affinity, class B transpeptidase involved in bacterial cell wall biosynthesis. It catalyzes the cross-linking of peptidoglycan chains, providing structural integrity to the bacterial cell wall. PBP4 contributes to β-lactam antibiotic resistance in certain bacteria, such as Enterococcus faecalis and Staphylococcus aureus, by maintaining transpeptidase activity even when other PBPs are inhibited. It contains a conserved active site with a catalytic serine residue that is acylated by β-lactam antibiotics, leading to inactivation. However, due to its low affinity, PBP4 can contribute to resistance.

β-lactam antibiotics inhibit PBP4 by acylating the active site serine residue, preventing peptidoglycan cross-linking.