5n9m

Crystal structure of GatD - a glutamine amidotransferase from Staphylococcus aureus involved in peptidoglycan amidation

spinqualitylabelsall models 5n9m, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5n9m is a 2 chain structure with sequence from Staphylococcus aureus subsp. aureus COL. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.85Å Ligands: GLN, PG4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GATD_STAAC The lipid II isoglutaminyl synthase complex catalyzes the formation of alpha-D-isoglutamine in the cell wall lipid II stem peptide (PubMed:22303291). The GatD subunit catalyzes the hydrolysis of glutamine to glutamate and ammonia. The resulting ammonia molecule is channeled to the active site of MurT (PubMed:29593310). Publication Abstract from PubMed Gram-positive bacteria homeostasis and antibiotic resistance mechanisms are dependent on the intricate architecture of the cell wall, where amidated peptidoglycan plays an important role. The amidation reaction is carried out by the bi-enzymatic complex MurT-GatD, for which biochemical and structural information is very scarce. In this work, we report the first crystal structure of the glutamine amidotransferase member of this complex, GatD from Staphylococcus aureus, at 1.85 A resolution. A glutamine molecule is found close to the active site funnel, hydrogen-bonded to the conserved R128. In vitro functional studies using (1)H-NMR spectroscopy showed that S. aureus MurT-GatD complex has glutaminase activity even in the absence of lipid II, the MurT substrate. In addition, we produced R128A, C94A and H189A mutants, which were totally inactive for glutamine deamidation, revealing their essential role in substrate sequestration and catalytic reaction. GatD from S. aureus and other pathogenic bacteria share high identity to enzymes involved in cobalamin biosynthesis, which can be grouped in a new sub-family of glutamine amidotransferases. Given the ubiquitous presence of GatD, these results provide significant insights into the molecular basis of the so far undisclosed amidation mechanism, contributing to the development of alternative therapeutics to fight infections. First insights of peptidoglycan amidation in Gram-positive bacteria - the high-resolution crystal structure of Staphylococcus aureus glutamine amidotransferase GatD.,Leisico F, V Vieira D, Figueiredo TA, Silva M, Cabrita EJ, Sobral RG, Ludovice AM, Trincao J, Romao MJ, de Lencastre H, Santos-Silva T Sci Rep. 2018 Mar 28;8(1):5313. doi: 10.1038/s41598-018-22986-3. PMID:29593310 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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