Format

Send to

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

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

Author information

1
Université Grenoble Alpes, CNRS, CEA, IBS UMR 5075, 38044, Grenoble, France.
2
Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, 1432, Norway.
3
Centre for Bacterial Cell Biology, Institute for Cell and Molecular Bioscience, Newcastle University, Newcastle Upon Tyne, NE2 4AX, United Kingdom.
4
Departamento de Química, Universidade Nova de Lisboa, Caparica, 2829-516, Portugal.
5
Membrane Biochemistry and Biophysics, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, 3584, The Netherlands.
6
Université Paris Descartes, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques UMR 8601 CNRS, Sorbonne Paris Cité (USPC), Paris, 75006, France.
7
Université Grenoble Alpes, CNRS, CEA, IBS UMR 5075, 38044, Grenoble, France. andre.zapun@ibs.fr.

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.

PMID:
30093673
PMCID:
PMC6085368
DOI:
10.1038/s41467-018-05602-w
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center