Which enzyme is inhibited by penicillin?
Bacterial peptidoglycan final crosslinking step catalyzed by transpeptidases penicillin binding proteins class B enzymes PBP2 for elongation, PBP3 FtsI for division. They cleave C terminal D alanine D alanine dipeptide from pentapeptide side chain MurNAc L Ala D Glu mDAP D Ala D Ala, forming acyl enzyme intermediate through active site serine nucleophile, then transfer to amino group acceptor meso diamino pimelic acid or L lysine of neighboring strand creating peptide crossbridge essential for wall rigidity. Beta lactam antibiotics penicillin contain four membered ring mimicking D Ala D Ala conformation fitting active site, acylating catalytic serine irreversibly forming stable penicilloyl enzyme unable to deacylate, blocking transpeptidation. Nascent peptidoglycan remains linear uncrosslinked degraded by endogenous autolysins lytic transglycosylases leading to osmotic lysis especially during growth when wall remodeling high. Gyrase target quinolones, RNA polymerase target rifampicin, ribosomal peptidyl transferase chloramphenicol. Thus penicillin specifically inhibits transpeptidase activity, mechanistic basis for bactericidal action and synergy with beta lactamase inhibitors clavulanate restoring efficacy against resistant strains.
Ref: Tipper & Strominger, PNAS 1965, Penicillin inhibits transpeptidase PBP crosslinking peptidoglycan.