Penicillin-binding protein (Mycobacterium tuberculosis) (PBP)

Penicillin-binding proteins (PBPs) are essential enzymes in Mycobacterium tuberculosis (Mtb) that catalyze the final stages of peptidoglycan biosynthesis, a critical component of the mycobacterial cell envelope (PMID: 21859865). These enzymes, categorized into high-molecular-weight (HMW) and low-molecular-weight (LMW) classes, function primarily as transpeptidases and carboxypeptidases to cross-link glycan strands, providing the cell wall with mechanical strength and osmotic protection (UniProt: P9WNE5). In Mtb, specific PBPs like PonA1 and PbpB (PBP3) are indispensable for cell elongation and septation during division (PMID: 25212885). While Mtb naturally produces a broad-spectrum beta-lactamase (BlaC) that confers resistance to many traditional penicillins, PBPs remain highly relevant therapeutic targets for carbapenems, which are relatively stable to BlaC or can be paired with inhibitors like clavulanate (PMID: 19244470). Targeting PBPs leads to the arrest of cell wall assembly, triggering autolytic pathways and bacterial death, making them pivotal in the strategy to combat drug-resistant tuberculosis (PMID: 28242633).

Other names

DD-transpeptidaseDD-carboxypeptidasePeptidoglycan synthasePonA1PbpBPbpADacBPBP1PBP3PBP4

Inhibition of the transpeptidase activity of penicillin-binding proteins, preventing the cross-linking of peptidoglycan chains and leading to cell wall instability and osmotic lysis.