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

Cécile Morlot, Daniel Straume, Katharina Peters, Olav A. Hegnar, Nolwenn Simon, Anne Marie Villard, Carlos Contreras-Martel, Francisco Leisico, Eefjan Breukink, Christine Gravier-Pelletier, Laurent Le Corre, Waldemar Vollmer, Nicolas Pietrancosta, Leiv Sigve Håvarstein, André Zapun

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number3180
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

Fingerprint Dive into the research topics of 'Structure of the essential peptidoglycan amidotransferase MurT/GatD complex from Streptococcus pneumoniae'. Together they form a unique fingerprint.

  • Cite this

    Morlot, C., Straume, D., Peters, K., Hegnar, O. A., Simon, N., Villard, A. M., ... Zapun, A. (2018). Structure of the essential peptidoglycan amidotransferase MurT/GatD complex from Streptococcus pneumoniae. Nature Communications, 9(1), [3180]. https://doi.org/10.1038/s41467-018-05602-w