Fig. 1.

The interplay among transpeptidase (TP), transglycosylase (TG), and Slt is depicted by the cartoons to the Left of each panel, explaining the mechanistic concept that emerged from the crystal structures shown to the Right of each panel. The NAM and NAG are depicted as dark and light green hexagons, respectively. The bicyclic anhNAM is in brown. The peptide stems are not shown, except for cross-links (black lines). The undecaprenyl membrane anchor of Lipid II is represented by the zigzagging black lines. (A) Lipid II is polymerized by a TG to generate the nascent peptidoglycan, which experiences cross-linking to the cell wall by a TP. On inhibition of TP by a β-lactam antibiotic, aberrant longer nascent peptidoglycan is formed, which serves as substrate for the endolytic reaction of Slt. (B) The product of endolytic reaction serves as substrate for the exolytic reaction of Slt, (C) which, in turn, generates the ultimate product, compound IIpa. Internalization of IIpa by the permease AmpG initiated the cascade of events that leads to production of β-lactamase as an antibiotic-resistance determinant against β-lactam antibiotics. The conceptual framework for the schematic was adapted from Cho et al. (4).