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Molecules 2012, 17(10), 11978-11989; doi:10.3390/molecules171011978
Article

The Binding Affinity and Molecular Basis of the Structure-Binding Relationship between Urinary Tamm-Horsfall Glycoprotein and Tumor Necrosis Factor-α

1,†, 2,†, 3, 3, 4, 5 and 3,*
1 Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, No.7 Chung-Shan South Road, Taipei 100, Taiwan 2 Institute of Clinical medicine, National Yang-Ming University College of Medicine, No.155 Li-Nong Street, Shih-Pai, Taipei 11217, Taiwan 3 Institute of Molecular Medicine, National Taiwan University College of Medicine, No.7 Chung-Shan South Road, Taipei 100, Taiwan 4 Section of Nephrology, Taipei Veterans General Hospital, No.201 Section 2, Shih-Pai Road, Taipei 11217, Taiwan 5 Section of Allergy, Immunology and Rheumatology, Taipei Veterans General Hospital, No.201 Section 2, Shih-Pai Road, Taipei 11217, Taiwan These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 13 July 2012 / Revised: 26 September 2012 / Accepted: 8 October 2012 / Published: 11 October 2012
(This article belongs to the Special Issue Advances in Carbohydrate Chemistry 2012)
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Abstract

In a previous study we noted significant THP binding to TNF-α, but did not explore the molecular basis of the structure-binding relationship. In this study, we used lectin-binding ELISA to assess the carbohydrate compositions of THP, BSA, IgG, TNF-α, and IFN-g. We identified β(1,4)-N-acetylglucosamine oligomers (GlcNAc) and GlcNAc/branched mannose in BSA, IgG, TNF-α, and THP, but not in IFN-g. These carbohydrate moieties mediated binding with THP. Small amounts of Siaα(2,3)Gal/ GalNAc, Sia(2,6)Gal/GalNAc, and mannose residues were also present in THP and TNF-α. Binding affinity (Kd) between THP and TNF-α by Scatchard plot analysis was 1.4–1.7 × 10−6 M, lower than antigen-antibody or ligand-receptor binding affinities. To elucidate the structure-binding relationship of THP-TNF-α, THP was digested with neuraminidase, β-galactosidase, O-sialoglycoprotein endopeptidase, carboxypeptidase Y, or proteinase K. β-galactosidase increased binding capacity of THP for TNF-α. Monosaccharide inhibition suggested that α-methyl-D-mannoside, GlcNAc, and GalNAc, but not sialic acid, suppress THP-TNF-α binding as detected by ELISA. We conclude that sugar-lectin and sugar-protein interactions between cognate sites in THP and TNF-α mediate their binding.
Keywords: Tamm-Horsfall glycoprotein; tumor necrosis factor-α; binding affinity; structure-binding relationship; glucosamine-containing mannose Tamm-Horsfall glycoprotein; tumor necrosis factor-α; binding affinity; structure-binding relationship; glucosamine-containing mannose
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Wu, C.-H.; Li, K.-J.; Siao, S.-C.; Chen, Y.-H.; Wu, T.-H.; Tsai, C.-Y.; Yu, C.-L. The Binding Affinity and Molecular Basis of the Structure-Binding Relationship between Urinary Tamm-Horsfall Glycoprotein and Tumor Necrosis Factor-α. Molecules 2012, 17, 11978-11989.

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