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Carbohydrate–Lectin Interactions: An Unexpected Contribution to Affinity
Author(s) -
Navarra Giulio,
Zihlmann Pascal,
Jakob Roman P.,
Stangier Katja,
Preston Roland C.,
Rabbani Said,
Smiesko Martin,
Wagner Bea,
Maier Timm,
Ernst Beat
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201600615
Subject(s) - bacterial adhesin , lectin , chemistry , ligand (biochemistry) , adhesion , glycoprotein , carbohydrate , biochemistry , escherichia coli , biophysics , microbiology and biotechnology , receptor , biology , gene , organic chemistry
Uropathogenic E. coli exploit PapG‐II adhesin for infecting host cells of the kidney; the expression of PapG‐II at the tip of bacterial pili correlates with the onset of pyelonephritis in humans, a potentially life‐threatening condition. It was envisaged that blocking PapG‐II (and thus bacterial adhesion) would provide a viable therapeutic alternative to conventional antibiotic treatment. In our search for potent PapG‐II antagonists, we observed an increase in affinity when tetrasaccharide 1 , the natural ligand of PapG‐II in human kidneys, was elongated to hexasaccharide 2 , even though the additional Siaα(2–3)Gal extension is not in direct contact with the lectin. ITC studies suggest that the increased affinity results from partial desolvation of nonbinding regions of the hexasaccharide; this is ultimately responsible for perturbation of the outer hydration layers. Our results are in agreement with previous observations and suggest a general mechanism for modulating carbohydrate–protein interactions based on nonbinding regions of the ligand.