Structure of the essential peptidoglycan amidotransferase MurT/GatD complex from Streptococcus pneumoniae

Nat Commun. 2018 Aug 9;9(1):3180. doi: 10.1038/s41467-018-05602-w.


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, we 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / metabolism
  • Bacterial Proteins / chemistry*
  • Catalytic Domain
  • Cell Wall / metabolism
  • Glutamic Acid / metabolism
  • Glutaminase / metabolism
  • Glutamine / metabolism
  • Lipids / chemistry
  • Mycobacterium tuberculosis / metabolism
  • Oxidoreductases / chemistry*
  • Peptidoglycan / chemistry*
  • Protein Domains
  • Staphylococcal Infections / metabolism
  • Staphylococcus aureus / metabolism
  • Streptococcus pneumoniae / enzymology*
  • Sulfhydryl Compounds / chemistry


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Lipids
  • Peptidoglycan
  • Sulfhydryl Compounds
  • Glutamine
  • Glutamic Acid
  • Oxidoreductases
  • Glutaminase