title: Structural basis for the specificity of basic winged bean lectin for the Tn-antigen: a crystallographic, thermodynamic and modelling study.
abstract: The crystal structure of winged bean basic agglutinin in complex with GalNAc-alpha-O-Ser (Tn-antigen) has been elucidated at 2.35 angstroms resolution in order to characterize the mode of binding of Tn-antigen with the lectin. The Gal moiety occupies the primary binding site and makes interactions similar to those found in other Gal/GalNAc specific legume lectins. The nitrogen and oxygen atoms of the acetamido group of the sugar make two hydrogen bonds with the protein atoms whereas its methyl group is stabilized by hydrophobic interactions. A water bridge formed between the terminal oxygen atoms of the serine residue of the Tn-antigen and the side chain oxygen atom of Asn128 of the lectin increase the affinity of the lectin for Tn-antigen compared to that for GalNAc. A comparison with the available structures reveals that while the interactions of the glyconic part of the antigen are conserved, the mode of stabilization of the serine residue differs and depends on the nature of the protein residues in its vicinity. The structure provides a qualitative explanation for the thermodynamic parameters of the complexation of the lectin with Tn-antigen. Modeling studies indicate the possibility of an additional hydrogen bond with the lectin when the antigen is part of a glycoprotein.
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, CVRaman Avenue, Bangalore, Karnataka 560 012, India.
authors.forename: Kiran A
authors.initials: KA
authors.lastname: Kulkarni
authors.forename: Sharmistha
authors.initials: S
authors.lastname: Sinha
authors.forename: Samiksha
authors.initials: S
authors.lastname: Katiyar
authors.forename: Avadhesha
authors.initials: A
authors.lastname: Surolia
authors.forename: Mamannamana
authors.initials: M
authors.lastname: Vijayan
authors.forename: Kaza
authors.initials: K
authors.lastname: Suguna
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism*; D001665:Binding Sites; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D019281:Dimerization; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D037102:Lectins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D037121:Plant Lectins / Q000737:chemistry* / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013059:Spectrum Analysis, Raman; D013379:Substrate Specificity; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D037102:Lectins; D037121:Plant Lectins; C040286:Tn antigen; C049304:winged bean lectin; D014867:Water