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Carbohydrate-Lectin Interactions - An Unexpected Contribution to Affinity

Navarra, Giulio and Zihlmann, Pascal and Jakob, Roman P. and Stangier, Katia and Preston, Roland C. and Rabbani, Said and Smiesko, Martin and Wagner, Bea and Maier, Timm and Ernst, Beat. (2017) Carbohydrate-Lectin Interactions - An Unexpected Contribution to Affinity. ChemBioChem, 18 (6). pp. 539-544.

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Official URL: http://edoc.unibas.ch/53270/

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Abstract

Uropathogenic E. coli exploit the PapG-II adhesin for infecting host cells of the kidney; moreover, the expression of PapG-II located at the tip of bacterial pili has been correlated with the onset of pyelonephritis in humans, a potentially life-threatening condition. It was envisaged that the blocking of PapG-II, and thus bacterial adhesion, embodies a viable therapeutic alternative to conventional antibiotic treatment. Within 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, although 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 non-binding regions of the hexasaccharide, and is ultimately connected to the perturbation of outer hydration layers. Our results are in agreement with previous observations and suggest a general mechanism for modulating carbohydrate-protein interactions based on non-binding regions of the ligand.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Maier)
05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molekulare Pharmazie (Ernst)
UniBasel Contributors:Maier, Timm and Zihlmann, Pascal and Jakob, Roman Peter and Stangier, Katja and Preston, Roland and Rabbani, Said and Smiesko, Martin and Wagner, Beatrice and Ernst, Beat
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wiley
ISSN:1439-4227
e-ISSN:1439-7633
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:28 Nov 2017 11:18
Deposited On:12 Oct 2017 06:56

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