Structural Basis for the Carbohydrate Specificities of Artocarpin: Variation in the Length of a Loop as a Strategy for Generating Ligand Specificity

• Published in: Journal of molecular biology Vol. 338; no. 4; pp. 757 - 770
• Main Authors: Jeyaprakash, A.Arockia, Srivastav, Anand, Surolia, A, Vijayan, M
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 07.05.2004
• Subjects: Binding Sites; Carbohydrate Conformation; Carbohydrate Sequence; carbohydrate specificity; crystal packing; Crystallography, X-Ray; Ligands; Mannose - chemistry; Mannose - metabolism; Mannose-Binding Lectins - chemistry; Mannose-Binding Lectins - genetics; Mannose-Binding Lectins - metabolism; Models, Molecular; Molecular Sequence Data; moraceae lectin; Plant Lectins - chemistry; Plant Lectins - genetics; Plant Lectins - metabolism; Protein Structure, Quaternary; Substrate Specificity; weak interactions; weak interactions; Mn3, mannotriose; carbohydrate conformation; Gn 2, GlcNAc2; moraceae lectin; crystal packing; carbohydrate specificity
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2004.03.040

Artocarpin, a tetrameric lectin of molecular mass 65 kDa, is one of the two lectins extracted from the seeds of jackfruit. The structures of the complexes of artocarpin with mannotriose and mannopentose reported here, together with the structures of artocarpin and its complex with Me-α-mannose reported earlier, show that the lectin possesses a deep-seated binding site formed by three loops. The binding site can be considered as composed of two subsites; the primary site and the secondary site. Interactions at the primary site composed of two of the loops involve mainly hydrogen bonds, while those at the secondary site comprising the third loop are primarily van der Waals in nature. Mannotriose in its complex with the lectin interacts through all the three mannopyranosyl residues; mannopentose interacts with the protein using at least three of the five mannose residues. The complexes provide a structural explanation for the carbohydrate specificities of artocarpin. A detailed comparison with the sugar complexes of heltuba, the only other mannose-specific jacalin-like lectin with known three-dimensional structure in sugar-bound form, establishes the role of the sugar-binding loop constituting the secondary site, in conferring different specificities at the oligosaccharide level. This loop is four residues longer in artocarpin than in heltuba, providing an instance where variation in loop length is used as a strategy for generating carbohydrate specificity.