Penicillin-binding protein 2; Penicillin-binding protein 3 (PBP2, PBP3)

Penicillin-binding proteins are a family of bacterial enzymes that catalyze the final stages of peptidoglycan cross-linking in the bacterial cell wall, which is essential for cell survival and shape maintenance. Specifically, PBP2 is critical for maintaining rod-shaped morphology and lateral wall elongation in Gram-negative bacteria, whereas PBP3 is essential for cell division (septation), and its inhibition results in filamentous (non-septate) bacteria. Both proteins are major targets of β-lactam antibiotics, which form a covalent acyl-enzyme complex with the active site serine, irreversibly inactivating these enzymes and ultimately leading to bacterial cell death. The essential nature and druggability of PBP2 and PBP3 underlie the clinical utility of β-lactam antibiotics against numerous pathogenic bacteria. Resistance mechanisms include mutations in PBP coding genes that lower drug affinity, and altered expression of PBPs or other enzymes.

Other names

PBP2E. coli penicillin-binding protein 2*pbpA* gene productPBP3E. coli penicillin-binding protein 3*ftsI* gene product

β-lactam antibiotics irreversibly acylate the active site serine of PBPs, forming a stable covalent acyl-enzyme complex and thereby inhibiting transpeptidase activity in cell wall synthesis, ultimately leading to bacterial cell lysis.