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Understanding the structural specificity of Tn antigen for its receptor: an NMR solution study.

D'Amelio, N; Coslovi, A; Rossi, M; Uggeri, F; Paoletti, S; (2012) Understanding the structural specificity of Tn antigen for its receptor: an NMR solution study. Carbohydr Res , 351 pp. 114-120. 10.1016/j.carres.2012.01.009.

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Abstract

The present work aims at understanding the structural basis of the biological recognition of Tn antigen (GalNAc-α-O-L-Ser), a specific epitope expressed by tumor cells, and the role of its amino acidic moiety in the interaction with its receptor (the isolectin B4 extracted from Vicia villosa). An NMR structural characterization of the α and β anomers, based on J couplings and molecular modeling revealed a structure in very good agreement with data reported in literature for variants of the same molecules. In order to demonstrate the involvement of the amino acid in the ligand-receptor recognition, also GalNAc-α-O-D-Ser was studied; the change in the stereochemistry is in fact expected to impact on the interaction only in case the serine is part of the epitope. Relaxation properties in the presence of the receptor clearly indicated a selective recognition of the natural L form, probably due to the formation of a water-mediated hydrogen bond with Asn 129 of the protein.

Type: Article
Title: Understanding the structural specificity of Tn antigen for its receptor: an NMR solution study.
Location: Netherlands
DOI: 10.1016/j.carres.2012.01.009
Keywords: Antigens, Tumor-Associated, Carbohydrate, Hydrogen Bonding, Isomerism, Magnetic Resonance Spectroscopy, Models, Molecular, Plant Lectins, Protein Conformation, Serine, Solutions, Substrate Specificity
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: http://discovery.ucl.ac.uk/id/eprint/1390917
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