Metal-Ion-Monosaccharide Interactions: Selective Formation of a Specific Coordination Motif in Carbohydrate...

Metal-ion-monosaccharide interactions play key roles in C-type lectins (CTLs), Ca²⁺-dependent carbohydrate-binding proteins responsible for selective carbohydrate recognition. Although monosaccharides adopt specific coordination motifs with metal ions in CTL binding sites, the factors governing which hydroxyl groups coordinate to the metal ion remain unclear. Here, we investigate the charge-density dependence of these interactions using cryogenic gas-phase infrared spectroscopy of alkali metal ion and Ca²⁺ complexes with methyl α-d-galactopyranoside and methyl α-d-mannopyranoside as ligands for CTLs. The spectra reveal systematic changes in coordination motifs with metal-ion charge density. Lower charge density favors a preferred motif supported by a strong intramolecular hydrogen-bond network, whereas higher charge density favors more highly coordinated structures that disrupt this network. Combined with quantum mechanical cluster calculations, these findings suggest that peptide coordination attenuates the effective charge density of Ca²⁺ in CTLs, thereby promoting formation of the coordination motif relevant to selective carbohydrate recognition.