title: Understanding the structural specificity of Tn antigen for its receptor: an NMR solution study.
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.
authors.affiliation: Bracco Imaging SpA-CRB Trieste, AREA Science Park, Building Q, SS 14, km 163.5, Basovizza, 34149 Trieste, Italy. ndamelio@cnio.es
authors.forename: Nicola
authors.initials: N
authors.lastname: D'Amelio
authors.forename: Anna
authors.initials: A
authors.lastname: Coslovi
authors.forename: Marco
authors.initials: M
authors.lastname: Rossi
authors.forename: Fulvio
authors.initials: F
authors.lastname: Uggeri
authors.forename: Sergio
authors.initials: S
authors.lastname: Paoletti
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry* / Q000378:metabolism*; D006860:Hydrogen Bonding; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D037121:Plant Lectins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D012694:Serine; D012996:Solutions; D013379:Substrate Specificity
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D037121:Plant Lectins; D012996:Solutions; C040286:Tn antigen; C042242:Vicia lectins; D012694:Serine