Structural basis of cell wall peptidoglycan amidation by the GatD/MurT complex of Staphylococcus aureus

Scientific Reports
Erik R NöldekeThilo Stehle

Abstract

The peptidoglycan of Staphylococcus aureus is highly amidated. Amidation of α-D-isoglutamic acid in position 2 of the stem peptide plays a decisive role in the polymerization of cell wall building blocks. S. aureus mutants with a reduced degree of amidation are less viable and show increased susceptibility to methicillin, indicating that targeting the amidation reaction could be a useful strategy to combat this pathogen. The enzyme complex that catalyzes the formation of α-D-isoglutamine in the Lipid II stem peptide was identified recently and shown to consist of two subunits, the glutamine amidotransferase-like protein GatD and the Mur ligase homolog MurT. We have solved the crystal structure of the GatD/MurT complex at high resolution, revealing an open, boomerang-shaped conformation in which GatD is docked onto one end of MurT. Putative active site residues cluster at the interface between GatD and MurT and are contributed by both proteins, thus explaining the requirement for the assembled complex to carry out the reaction. Site-directed mutagenesis experiments confirm the validity of the observed interactions. Small-angle X-ray scattering data show that the complex has a similar conformation in solution, although some movem...Continue Reading

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Citations

Jun 12, 2019·FEMS Microbiology Reviews·Arundhati MaitraSanjib Bhakta
Jul 31, 2019·Antimicrobial Agents and Chemotherapy·Bárbara V GonçalvesRita G Sobral
Jul 28, 2019·International Journal of Medical Microbiology : IJMM·Sandra UnsleberEvi Stegmann
Aug 7, 2019·International Journal of Medical Microbiology : IJMM·Erik R Nöldeke, Thilo Stehle
Dec 30, 2020·Chemical Reviews·Jed F Fisher, Shahriar Mobashery

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Methods Mentioned

BETA
transglycosylation
amidation
X-ray
size exclusion chromatography
PISA
Thin-layer chromatography
circular dichroism
co-crystallization
PCR
Protein

Software Mentioned

GatD
SREFLEX
autoSHARP
EPPIC
MAFFT
REFINE
XDS
HHPRED
AutoBuild Wizard
PISA

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