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Lookup NU author(s): Dr Katharina Pazos Don Pedro,
Professor Waldemar Vollmer
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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.
Author(s): Morlot C, Straume D, Peters K, Hegnar OA, Simon N, Villard AM, Contreras-Martel C, Leisico F, Breukink E, Gravier-Pelletier C, LeCorre L, Vollmer W, Pietrancosta N, Håvarstein LS, Zapun A
Publication type: Article
Publication status: Published
Journal: Nature Communications
Online publication date: 09/08/2018
Acceptance date: 17/07/2018
Date deposited: 17/07/2018
ISSN (electronic): 2041-1723
Publisher: Nature Publishing Group
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