Structure of MltG from Mycobacterium abscessus reveals structural plasticity between composed domains

Abstract

We provide the structure of MltG of the lytic transglycosyl­ase family in this study. We show that MltG has a flexible peptidoglycan-binding domain and exists as a monomer in solution. Further, the putative active site of Mycobacterium abscessus MltG has been revealed using structural analysis and sequence comparison. This research significantly advances our comprehension of the transglycosyl­ation process mediated by the MltG family, providing valuable insights that can inform the development of next-generation antibiotics to specifically target M. abscessus.

MltG, a membrane-bound lytic transglycosyl­ase, has roles in terminating glycan polymerization in peptidoglycan and incorporating glycan chains into the cell wall, making it significant in bacterial cell-wall biosynthesis and remodeling. This study provides the first reported MltG structure from Mycobacterium abscessus (maMltG), a superbug that has high antibiotic resistance. Our structural and biochemical analyses revealed that MltG has a flexible peptidoglycan-binding domain and exists as a monomer in solution. Further, the putative active site of maMltG was disclosed using structural analysis and sequence comparison. Overall, this study contributes to our understanding of the transglycosyl­ation reaction of the MltG family, aiding the design of next-generation antibiotics targeting M. abscessus.