Targeting the Bacterial Transglycosylase: Antibiotic Development from a Structural Perspective.

One of the major threats to human life nowadays is widespread antibiotic resistance. Antibiotics are used to treat bacterial infections by targeting their essential pathways, such as the biosynthesis of bacterial cell walls. Bacterial transglycosylase, particularly glycosyltransferase family 51 (GT51), is one critical player in the cell wall biosynthesis and has long been known as a promising yet challenging target for antibiotic development. Here, we review the structural studies of this protein and summarize recent progress in developing its specific inhibitors, including synthetic substrate analogs and novel compounds identified from high-throughput screens. A detailed analysis of the protein-ligand interface has also provided us with valuable insights into the future antibiotic development against the bacterial transglycosylase.