Peptidoglycan D,D-transpeptidase MrdA (PBP2) (PBP2)

Peptidoglycan D,D-transpeptidase MrdA, commonly known as Penicillin-binding protein 2 (PBP2), is an essential enzyme in Escherichia coli responsible for the synthesis and cross-linking of the peptidoglycan layer, specifically during cell elongation (UniProt P0AD65). Encoded by the mrdA gene, it is a Class B high-molecular-mass PBP that functions as a D,D-transpeptidase (PubMed 30995398). PBP2 is critical for maintaining the characteristic rod shape of E. coli; its inhibition or inactivation leads to the formation of spherical cells and eventual bacterial lysis (PubMed 1103132). It is the primary target of the beta-lactam antibiotic mecillinam (amdinocillin), which binds covalently to the active site serine to block enzyme activity (PubMed 3009484). Beyond its catalytic role, PBP2 is part of the elongasome complex and interacts with other proteins like RodA to coordinate cell wall growth (PubMed 12519203). Resistance to drugs targeting PBP2 can arise through mutations in the mrdA gene or through the action of beta-lactamases that degrade the antibiotics before they reach the target (PubMed 31939154).

Other names

Penicillin-binding protein 2PBP-2MrdATranspeptidase PBP2Class B penicillin-binding protein 2

Covalent inhibition of transpeptidase activity by acylating the active site serine residue (Ser330), preventing peptidoglycan cross-linking and leading to cell wall instability, spherical cell morphology, and lysis (UniProt P0AD65, PubMed 30995398).