Journal
CHEMBIOCHEM
Volume 18, Issue 6, Pages 539-544Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201600615
Keywords
antiadhesive; PapG; pyelonephritis; thermodynamics; X-ray diffraction
Funding
- Swiss National Science Foundation [R'EQUIP 145023]
- SNF: Marie Heim-Vogtlin-Promotion of Women
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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 Sia(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.
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