Investigation of Protein and Inhibitor Binding to O-Acetylpeptidoglycan Esterase 1 from Neisseria gonorrhoeae

Abstract

O-Acetylpeptidoglycan esterase 1 (Ape1) is a periplasmic esterase present in pathogenic organisms that produce O-acetylated peptidoglycan. Ape1a plays a crucial role in the growth of these bacteria by regulating the turnover of peptidoglycan through catalytic removal of the C-6 acetyl group of the modified peptidoglycan. Specifically, Ape1a activity is necessary for peptidoglycan turnover by the main autolytic enzymes, lytic transglycosylases (LTs); LTs are blocked by the presence of an acetyl group on the C-6 hydroxyl of N-acetylmuramic acid. Purpurin has been observed to inhibit the esterase activity of Ape1 in vitro and inhibits the growth of bacteria that produce O-acetylpeptidoglycan. This study found that Ape1 binds to FtsZ in a presumed multi-enzyme complex. The 2-hydroxyl group of anthraquinones, such as purpurin or alizarin, needs to be deprotonated to work as a suitable inhibitor of Ape1. Purpurin was demonstrated to work synergistically with aminoglycosides against Bacillus cereus species.