Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Binding of the Bacterial Adhesin FimH to Its Natural, Multivalent High-Mannose Type Glycan Targets.
Journal, issue, pages	J Am Chem Soc, Vol. 141, Issue 2, Page 936-944, Year 2019
Publish date	Jan 16, 2019
Authors	Maximilian M Sauer / Roman P Jakob / Thomas Luber / Fabia Canonica / Giulio Navarra / Beat Ernst / Carlo Unverzagt / Timm Maier / Rudi Glockshuber /
PubMed Abstract	Multivalent carbohydrate-lectin interactions at host-pathogen interfaces play a crucial role in the establishment of infections. Although competitive antagonists that prevent pathogen adhesion are ...Multivalent carbohydrate-lectin interactions at host-pathogen interfaces play a crucial role in the establishment of infections. Although competitive antagonists that prevent pathogen adhesion are promising antimicrobial drugs, the molecular mechanisms underlying these complex adhesion processes are still poorly understood. Here, we characterize the interactions between the fimbrial adhesin FimH from uropathogenic Escherichia coli strains and its natural high-mannose type N-glycan binding epitopes on uroepithelial glycoproteins. Crystal structures and a detailed kinetic characterization of ligand-binding and dissociation revealed that the binding pocket of FimH evolved such that it recognizes the terminal α(1-2)-, α(1-3)-, and α(1-6)-linked mannosides of natural high-mannose type N-glycans with similar affinity. We demonstrate that the 2000-fold higher affinity of the domain-separated state of FimH compared to its domain-associated state is ligand-independent and consistent with a thermodynamic cycle in which ligand-binding shifts the association equilibrium between the FimH lectin and the FimH pilin domain. Moreover, we show that a single N-glycan can bind up to three molecules of FimH, albeit with negative cooperativity, so that a molar excess of accessible N-glycans over FimH on the cell surface favors monovalent FimH binding. Our data provide pivotal insights into the adhesion properties of uropathogenic Escherichia coli strains to their target receptors and a solid basis for the development of effective FimH antagonists.
External links	J Am Chem Soc / PubMed:30543411
Methods	X-ray diffraction
Resolution	1.719 - 2.501 Å
Structure data	PDB-6gtv: Crystal structure of a FimHDsG complex from E.coli F18 with bound trimannose* Method: X-RAY DIFFRACTION / Resolution: 2.1 Å PDB-6gtw: Crystal structure of the FimH lectin domain from E.coli F18 in complex with trimannose Method: X-RAY DIFFRACTION / Resolution: 2.5 Å PDB-6gtx: Crystal structure of the FimH lectin domain from E.coli K12 in complex with the dimannoside Man(alpha1-2)Man Method: X-RAY DIFFRACTION / Resolution: 2.5 Å PDB-6gty: Crystal structure of the FimH lectin domain from E.coli K12 in complex with the dimannoside Man(alpha1-6)Man Method: X-RAY DIFFRACTION / Resolution: 1.9 Å PDB-6gtz: Crystal structure of a FimHDsG complex from E.coli F18 with bound dimannoside Man(alpha1-3)Man in space group P21* Method: X-RAY DIFFRACTION / Resolution: 1.719 Å PDB-6gu0: Crystal structure of a FimHDsG complex from E.coli F18 with bound dimannoside Man(alpha1-3)Man in space group P213* Method: X-RAY DIFFRACTION / Resolution: 2.501 Å
Chemicals	ChemComp-PEG: DI(HYDROXYETHYL)ETHER ChemComp-1PE: PENTAETHYLENE GLYCOL / precipitantYM ChemComp-HOH: WATER ChemComp-CA: Unknown entry ChemComp-SO4*: SULFATE ION
Source	escherichia coli f18+ (bacteria) escherichia coli 536 (bacteria) escherichia coli (strain k12) (bacteria) escherichia coli k-12 (bacteria)
Keywords	CELL ADHESION / TYPE I PILUS / CATCH-BOND / LECTIN / UPEC / INFECTION / MANNOSE