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Taxonomic group: bacteria / Proteobacteria (Phylum: Proteobacteria)
Associated disease: infection due to Escherichia coli [ICD11: XN6P4

]

NCBI PubMed ID: 23184990
Publication DOI: 10.1073/pnas.1209253109
Journal NLM ID: 7505876
Publisher: National Academy of Sciences
Correspondence: sml

fz-borstel.de; svevans

uvic.ca
Institutions: Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada V8P 3P6, Research Center Borstel, Leibniz Center for Medicine and Biosciences, Medical and Biochemical Microbiology, D-23845 Borstel, Germany, Department of Biochemistry, Membrane Protein Disease Research Group, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada T6G 2H7, Department of Chemistry, University of Natural Resources and Life Sciences, A-1190 Vienna, Austria, Novartis Institutes for BioMedical Research, 4002 Basel, Switzerland

Escherichia coli infections, a leading cause of septic shock, remain a major threat to human health because of the fatal action to endotoxin (LPS). Therapeutic attempts to neutralize endotoxin currently focus on inhibiting the interaction of the toxic component lipid A with myeloid differentiating factor 2, which forms a trimeric complex together with Toll-like receptor 4 to induce immune cell activation. The 1.73-A resolution structure of the unique endotoxin-neutralizing protective antibody WN1 222-5 in complex with the core region shows that it recognizes LPS of all E. coli serovars in a manner similar to Toll-like receptor 4, revealing that protection can be achieved by targeting the inner core of LPS and that recognition of lipid A is not required. Such interference with Toll-like receptor complex formation opens new paths for antibody sepsis therapy independent of lipid A antagonists.

structure, Escherichia coli, antibody, recognition, binding, Toll-like receptor 4

Structure type: oligomer
Location inside paper: p.20878, fig.1A, E. coli R2 dodecasaccharide-P4
Compound class: core oligosaccharide
Contained glycoepitopes: IEDB_130650,IEDB_130659,IEDB_130670,IEDB_133751,IEDB_135394,IEDB_136906,IEDB_137472,IEDB_140088,IEDB_140529,IEDB_141794,IEDB_141807,IEDB_142488,IEDB_144998,IEDB_146664,IEDB_150908,IEDB_151528,IEDB_151531,IEDB_179937,IEDB_190606,IEDB_2189047,IEDB_226811,IEDB_232584,IEDB_983931,SB_192,SB_7

Methods: ELISA, serological methods, crystallization
Comments, role: E. coli (R2 core type) dodecasaccharide-P4
3D data: 3D data

NCBI Taxonomy refs (TaxIDs): 1197131
Reference(s) to other database(s): GlycomeDB:26765
Show glycosyltransferases

There is only one chemically distinct structure:

N[C@H]1[C@@H](O[C@@H]2[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]2O[C@@H]2[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]2O[C@H]2[C@H](O)[C@@H](CO[C@H]3O[C@H](CO)[C@H](O)[C@H](O)[C@H]3O)O[C@H](O[C@@H]3[C@H](O)[C@@H](O[C@@H]4[C@H](O)[C@@H](O[C@@H]5[C@H](O[C@]6(C(=O)O)C[C@@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O6)C[C@](OC[C@H]6O[C@@H](OC[C@H]7O[C@H](OP(=O)(O)O)[C@H](N)[C@@H](O)[C@@H]7O)[C@H](N)[C@@H](O)[C@@H]6OP(=O)(O)O)(C(=O)O)O[C@@H]5[C@H](O)CO)O[C@H]([C@@H](O)CO)[C@H]4OP(=O)(O)O)O[C@H]([C@@H](O)CO[C@H]4O[C@H]([C@@H](O)CO)[C@@H](O)[C@H](O)[C@@H]4O)[C@H]3OP(=O)(O)O)[C@@H]2O)O[C@H](CO)[C@@H](O)[C@@H]1O

SVG MW SMILES 3D mol Ionize