Influence of glycosidic linkage on the nature of carbohydrate binding in β-prism I fold lectins: An X-ray and molecular dynamics investigation on banana lectin–carbohydrate complexes

Abstract

The three crystal structures reported here provide details of the interactions of mannose and the mannosyl-α-1,3-mannose component of a pentamannose with banana lectin and evidence for the binding of glucosyl-α-1,2-glucose to the lectin. The known structures involving the lectin include a complex with glucosyl-β-1,3-glucose. Modeling studies on the three disaccharide complexes with the reducing end and the nonreducing end at the primary binding site are also provided here. The results of the X-ray and modeling studies show that the disaccharides with an α-1,3 linkage prefer to have the nonreducing end at the primary binding site, whereas the reducing end is preferred at the site when the linkage is β-1,3 in mannose/glucose-specific β-prism I fold lectins. In the corresponding galactose-specific lectins, however, α-1,3-linked disaccharides cannot bind the lectin with the nonreducing end at the primary binding site on account of steric clashes with an aromatic residue that occurs only when the lectin is galactose-specific. Molecular dynamics simulations based on the known structures involving banana lectin enrich the information on lectin-carbohydrate interactions obtained from crystal structures. They demonstrate that conformational selection as well as induced fit operate when carbohydrates bind to banana lectin.

Structural Basis for Multiple Sugar Recognition of Jacalin-related Human ZG16p Lectin

“…The β-prism-fold consists of three β-sheets and each is made up of three to four β-strands. The human ZG16p structure is similar to those of the other Jacalin-related mannose-binding lectins: Banlec (17), Heltuba (18), Atrocarpin (19), MornigaM (20), Parkia lectin (21), and Griffithsin (22). These lectins do not require Ca 2+ ions for mannose binding and their carbohydrate-binding sites consist of three exposed loops, GG loop, recognition loop, and binding loop at the top of the β-prism I-fold (23).…”

“…The short α-mannose glycans bound have the Manα1–3Man unit in common, whereas the pauci and high mannose N -glycans having terminal Manα1–3Man unit did not give strong signals. For comparison, we performed the same microarray analysis using the well characterized mannose-binding β-prism lectin, Banlec (17). In contrast to ZG16p, Banlec bound to most of the pauci and high mannose N -glycans (Fig.…”

Structural diversity and ligand specificity of lectins. The Bangalore effort

“…It was hypothesized that β(1-3) linked disaccharides with the non-reducing end at the primary binding site would lead to steric clashes of the second sugar residue with secondary binding site A in jacalin. The issue came into sharper focus when the complexes of banana lectin with Man α(1-3) Man and Glc β(1-3) Glc (laminaribose) were compared [51,53]. The non-reducing end occupies the primary binding site in the mannobiose complex while the reducing end does in the laminaribose complex (Fig.…”

“…Therefore Man and Glc are expected to behave in the same manner with respect to binding to the lectin. The difference in the behavior of the two disaccharides in their orientation when bound to the lectin could be explained in terms of detailed modeling [53]. The importance of the anomeric nature of the glycosidic linkage on the orientation of the bound sugar could be of significance in determining the affinity of lectins to glyoproteins and other glycoconjugates.…”

“…The MD simulations carried out on some β-prism I fold lectins, including those on the sugar complexes of jacalin [57] and banana lectin [53], provide insights into the issue relating to conformational selection and induced fit. In the context of ligand binding, conformational selection involves the utilization of those conformations that are most appropriate for the ligand, from an ensemble of possible conformations.…”