Penicillin-binding proteins

All β-lactam antibiotics (except for tabtoxinine-β-lactam, which inhibits glutamine synthetase) bind to PBPs, which are essential for bacterial cell wall synthesis.

Low Molecular-Mass (LMM) PBP’s are dispensable for normal cell growth and control how tightly the peptidoglycan chains are linked together.

[6] PBPs are all involved in the final stages of the synthesis of peptidoglycan, which is the major component of bacterial cell walls.

[3] The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (involved in formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (involved in cross-linking of the peptide subunits) and the serine at the active site is conserved in all members of the PBP family.

[8] In contrast, high-molecular-weight PBPs are independent from MreB and maintain cell wall integrity by detecting and repairing defects in the peptidoglycan.

[9] PBPs bind to β-lactam antibiotics because they are similar in chemical structure to the modular pieces that form the peptidoglycan.

[13] Penicillin binding protein 3 is important for bacteria wall synthesis and is a main target in β-lactam antibiotics.

[5] The active site is located in a long cleft running parallel with the 3 strand across the lower part of the transpeptidase domain.

Ribbon representation of the atomic structure of Penicillin Binding Protein 3 from Pseudomonas aeruginosa (PDB 3OC2) , [ 1 ] image created with PyMol .
PBPs normally catalyze the cross-linking of the bacterial cell wall, but they can be permanently inhibited by penicillin and other β-lactam antibiotics. (NAM = N-acetylmuramic acid; NAG = N-acetylglucosamine) [ 2 ]
This image shows the active site of Penicillin Binding Protein 3 with carbenicillin in the active site (colored in pink with red, blue, and yellow representing different atoms). The serine residue positioned at 294,is covalently bound to the carbenicillin. This creates hydrogen bonding interactions between carboxylate groups on the carbenicillin and amino acid residues, N351, S485, and T487. (PBD - 3OCL)