Crystallographic, thermodynamic, and molecular modeling studies of the mode of binding of oligosaccharides to the potent antiviral protein griffithsin

The mode of binding of oligosaccharides to griffithsin, ark antiviral lectin from the red alga Griffithsia sp., wits investigated by a combination of X-ray crystallography, isothermal titration calorimetry, and molecular modeling. The structures of complexes of griffithsin with 1 -> 6 alpha-mannobiose and With maltose were solved and refined at the resolution of 2.0 and 1.5 angstrom, respectively. The thermodynamic parameters of binding of 1 -> 6 alpha-mannobiose, maltose, and mannose to griffithsin were determined. Binding profiles of 1 6 alpha-mannobiose and mainnose were similar with K-d values of 83.3 mu M and 102 mu M, respectively. The binding of maltose to griffithsin was significantly weaker, with a fourfold lower affinity,(K-d = 394 mu M). In all cases the binding at 30 degrees C was entropically rather than enthalpically driven. On the basis of the experimental crystal structures, as well as on previously determined structures of complexes with monosaccharides, it was possible to create a model of a tridentate complex of griffithsin with MangGIcNAC(2), a high mannose oligosaccharide commonly found on the surface of viral glycoproteins. All shorter oligomannoses could be modeled only as bidentate or monodentate complexes with griffithsin. The ability to mediate tight multivalent and multisite interactions with high-mannose oligosaccharides helps to explain the potent antiviral activity of griffithsin.

See More