title: Structural basis of bacterial defense against g-type lysozyme-based innate immunity.
abstract: Gram-negative bacteria can produce specific proteinaceous inhibitors to defend themselves against the lytic action of host lysozymes. So far, four different lysozyme inhibitor families have been identified. Here, we report the crystal structure of the Escherichia coli periplasmic lysozyme inhibitor of g-type lysozyme (PliG-Ec) in complex with Atlantic salmon g-type lysozyme (SalG) at a resolution of 0.95 Å, which is exceptionally high for a complex of two proteins. The structure reveals for the first time the mechanism of g-type lysozyme inhibition by the PliG family. The latter contains two specific conserved regions that are essential for its inhibitory activity. The inhibitory complex formation is based on a double 'key-lock' mechanism. The first key-lock element is formed by the insertion of two conserved PliG regions into the active site of the lysozyme. The second element is defined by a distinct pocket of PliG accommodating a lysozyme loop. Computational analysis indicates that this pocket represents a suitable site for small molecule binding, which opens an avenue for the development of novel antibacterial agents that suppress the inhibitory activity of PliG.
authors.affiliation: Laboratory for Biocrystallography, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, Herestraat 49 bus 822, 3000, Leuven, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Leysen
authors.forename: L
authors.initials: L
authors.lastname: Vanderkelen
authors.forename: S D
authors.initials: SD
authors.lastname: Weeks
authors.forename: C W
authors.initials: CW
authors.lastname: Michiels
authors.forename: S V
authors.initials: SV
authors.lastname: Strelkov
mesh_terms: D000818:Animals; D003461:Crystallography; D004926:Escherichia coli / Q000737:chemistry* / Q000276:immunology; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D007113:Immunity, Innate / Q000276:immunology*; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D020317:Salmo salar
chemical_list: D029968:Escherichia coli Proteins; C558304:PliG protein, E coli; D009113:Muramidase