The universality of peptidoglycan in bacteria underlies the broad spectrum of many successful antibiotics. However, in our times of widespread resistance, the diversity of peptidoglycan modifications offers a variety of new antibacterials targets. In some Gram-positive species such as Streptococcus pneumoniae, Staphylococcus aureus, or Mycobacterium tuberculosis, the second residue of the peptidoglycan precursor, D-glutamate, is amidated into iso-D-glutamine by the essential amidotransferase MurT/GatD complex. Here, IBS/PG researchers in collaboration with the Norwegian University of Life Sciences, Newcastle University, Universidade Nova de Lisboa, Utrecht University and Université Paris Descartes, present the structure of this complex at 3.0 Å resolution. MurT has central and C-terminal domains similar to Mur ligases with a cysteine-rich insertion, which probably binds zinc, contributing to the interface with GatD. The mechanism of amidation by MurT is likely similar to the condensation catalyzed by Mur ligases. GatD is a glutaminase providing ammonia that is likely channeled to the MurT active site through a cavity network. The structure and assay presented here constitute a knowledge base for future drug development studies.
Structure of the essential peptidoglycan amidotransferase MurT/GatD complex from Streptococcus pneumoniae. Morlot C, Straume D, Peters K, Hegnar OA, Simon N, Villard AM, Contreras-Martel C, Leisico F, Breukink E, Gravier-Pelletier C, Le Corre L, Vollmer W, Pietrancosta N, Håvarstein LS, Zapun A. Nature Communcations ;9(1):3180