Penicillin-binding protein 2 (MrdA) (PBP2)

Penicillin-binding protein 2 (PBP2), encoded by the mrdA gene, is a critical enzyme involved in the biosynthesis of the bacterial cell wall, particularly in Gram-negative organisms like Escherichia coli [UniProt: P0AD65, NIH: PMC6581181]. As a member of the class B high-molecular-weight penicillin-binding proteins, it possesses DD-transpeptidase activity, which is essential for cross-linking peptidoglycan strands to provide structural integrity to the cell [RCSB PDB: PBP, Wikipedia: Penicillin-binding proteins]. PBP2 plays a specialized role in cell elongation and the maintenance of the characteristic rod shape of bacteria, functioning as part of a multi-protein complex that includes RodA and the MreB cytoskeleton [UniProt: P0AD65, NIH: PMC6581181]. Due to its essential nature and its location on the periplasmic side of the inner membrane, PBP2 is a primary target for several classes of antibiotics, most notably beta-lactams like mecillinam and carbapenems [UniProt: P0AD65, NIH: PMC6581181]. These drugs act by covalently binding to the active site serine of the enzyme, thereby halting cell wall synthesis and triggering bacterial cell lysis [RCSB PDB: PBP, NIH: PMC4924382]. Clinical resistance to these agents often arises through mutations in the mrdA gene, which reduce the affinity of the protein for the antibiotics [NIH: PMC6581181]. Furthermore, PBP2 is involved in the regulation of other cell wall-related processes and its inhibition can lead to significant morphological changes, such as the transition from rod-shaped to spherical cells [UniProt: P0AD65].

Other names

PBP-2Peptidoglycan D,D-transpeptidase MrdATranspeptidase PBP2mrdA gene productRod shape-determining protein PBP2

Inhibition of the transpeptidase activity by covalent binding to the active site serine residue, preventing the cross-linking of peptidoglycan strands and leading to bacterial cell lysis [RCSB PDB: PBP, NIH: PMC4924382].