3lat

Crystal structure of Staphylococcus peptidoglycan hydrolase AmiE

spinqualitylabelsall models 3lat, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3lat is a 2 chain structure with sequence from Staphylococcus epidermidis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BU1, CL, IMD, ZN Gene: atlE (Staphylococcus epidermidis) Activity: N-acetylmuramoyl-L-alanine amidase, with EC number 3.5.1.28 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The major autolysins (Atl) of Staphylococcus epidermidis and S. aureus play an important role in cell separation, and their mutants are also attenuated in virulence. Therefore, autolysins represent a promising target for the development of new types of antibiotics. Here, we report the high-resolution structure of the catalytically active amidase domain AmiE (amidase S. epidermidis) from the major autolysin of S. epidermidis. This is the first protein structure with an amidase-like fold from a bacterium with a gram-positive cell wall architecture. AmiE adopts a globular fold, with several alpha-helices surrounding a central beta-sheet. Sequence comparison reveals a cluster of conserved amino acids that define a putative binding site with a buried zinc ion. Mutations of key residues in the putative active site result in loss of activity, enabling us to propose a catalytic mechanism. We also identified and synthesized muramyltripeptide, the minimal peptidoglycan fragment that can be used as a substrate by the enzyme. Molecular docking and digestion assays with muramyltripeptide derivatives allow us to identify key determinants of ligand binding. This results in a plausible model of interaction of this ligand not only for AmiE, but also for other PGN-hydrolases that share the same fold. As AmiE active-site mutations also show a severe growth defect, our findings provide an excellent platform for the design of specific inhibitors that target staphylococcal cell separation and can thereby prevent growth of this pathogen. Structural basis of cell wall cleavage by a staphylococcal autolysin.,Zoll S, Patzold B, Schlag M, Gotz F, Kalbacher H, Stehle T PLoS Pathog. 2010 Mar 12;6(3):e1000807. PMID:20300605 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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