3LAT
Crystal structure of Staphylococcus peptidoglycan hydrolase AmiE
Summary for 3LAT
| Entry DOI | 10.2210/pdb3lat/pdb |
| Descriptor | Bifunctional autolysin, IMIDAZOLE, ZINC ION, ... (6 entities in total) |
| Functional Keywords | amidase, atle, autolysin, peptidoglycan hydrolase, cell wall biogenesis/degradation, multifunctional enzyme, secreted, hydrolase |
| Biological source | Staphylococcus epidermidis |
| Cellular location | Secreted: O33635 |
| Total number of polymer chains | 2 |
| Total formula weight | 50093.37 |
| Authors | Zoll, S.,Stehle, T. (deposition date: 2010-01-07, release date: 2010-03-23, Last modification date: 2024-03-20) |
| Primary citation | Zoll, S.,Patzold, B.,Schlag, M.,Gotz, F.,Kalbacher, H.,Stehle, T. Structural basis of cell wall cleavage by a staphylococcal autolysin Plos Pathog., 6:e1000807-e1000807, 2010 Cited by PubMed Abstract: 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. PubMed: 20300605DOI: 10.1371/journal.ppat.1000807 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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