Penicillin Binding Proteins: An Insight Into Novel Antibacterial Drug Target

Abstract- Penicillin binding proteins (PBP) have been analysed for over 40 years. PBPs are the enzymes that catalyze the synthesis of peptidoglycan in bacteria.The peptidoglycan is made of glycan chains of alternating N-acetyl glucosamine and N-acetylmuramic acid, cross-linked by short stem peptides attached to the N-acetylmuramic acid. Peptidoglycan enables the bacteria to resist the intracellular pressure of several atmospheres and provides shape to the bacterial cell and isreproduced from generation togeneration. Also bacterial cell division requires the biosynthesis of peptidoglycan by PBPs during cell wall elongation and septum formation. These PBPs are divided into three classes based on their functions. The high molecular weight (HMW) PBPs that are divided into class A and class B whichplay bifunctional roles, transpeptidases (the cross-linking between glycan chains)/transglycosylases (polymerization of the glycan strand) and monofunctional transpeptidases, respectively. Some PBPs hydrolyze the last D-alanine of the stem peptide (DD-carboxypeptidation) or hydrolyze the peptide bond connecting two glycan strands (endopeptidation).The low molecular weight (LMW) PBPs are included in Class C. Because of the structural resemblance between PBPs natural substrate, the D-Ala-D-Ala end of the stem peptides and penicillin, the late stage peptidoglycan synthesizing enzymes are sensitive to penicillin with which they form a long-lived acyl-enzyme that impairs their peptidoglycan cross-linking capability. This review article focuses on detailed insight on PBP classification and mechanism, thus opening avenues for an effective and novel antibacterial drug target research and therapy.