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

Area of Science:

• Biochemistry
• Structural Biology
• Microbiology

Background:

• Peptidoglycan is a universal bacterial cell wall component and a target for broad-spectrum antibiotics.
• Increasing antibiotic resistance necessitates exploring novel antibacterial targets, including peptidoglycan modifications.
• The MurT/GatD complex is essential for amidating D-glutamate to iso-D-glutamine in Gram-positive bacteria like S. pneumoniae and M. tuberculosis.

Purpose of the Study:

• To elucidate the structure of the essential MurT/GatD amidotransferase complex.
• To provide insights into the mechanism of peptidoglycan precursor amidation.
• To establish a knowledge base for future antibacterial drug development.

Main Methods:

• X-ray crystallography was used to determine the structure of the MurT/GatD complex at 3.0 Å resolution.
• Biochemical assays were performed to investigate the complex's function.

Main Results:

• The 3.0 Å resolution structure of the MurT/GatD complex was determined.
• MurT exhibits domains similar to Mur ligases, with a cysteine-rich insertion potentially binding zinc and mediating interaction with GatD.
• GatD functions as a glutaminase, supplying ammonia likely channeled to MurT's active site via a network of cavities.

Conclusions:

• The determined structure provides a detailed view of the MurT/GatD complex, essential for bacterial cell wall biosynthesis.
• Understanding the amidation mechanism offers a basis for designing novel inhibitors.
• This structural knowledge is critical for developing new antibacterial strategies against resistant pathogens.