Energetics of galactose– and glucose–aromatic amino acid interactions: Implications for binding in galactose‐specific proteins

Abstract

An aromatic amino acid is present in the binding site of a number of sugar binding proteins. The interaction of the saccharide with the aromatic residue is determined by their relative position as well as orientation. The position-orientation of the saccharide relative to the aromatic residue was found to vary in different sugar-binding proteins. In the present study, interaction energies of the complexes of galactose (Gal) and of glucose (Glc) with aromatic residue analogs have been calculated by ab initio density functional (U-B3LYP/ 6-31G**) theory. The position-orientations of the saccharide with respect to the aromatic residue observed in various Gal-, Glc-, and mannose-protein complexes were chosen for the interaction energy calculations. The results of these calculations show that galactose can interact with the aromatic residue with similar interaction energies in a number of position-orientations. The interaction energy of Gal-aromatic residue analog complex in position-orientations observed for the bound saccharide in Glc/Man-protein complexes is comparable to the Glc-aromatic residue analog complex in the same position-orientation. In contrast, there is a large variation in interaction energies of complexes of Glc-and of Gal-with the aromatic residue analog in position-orientations observed in Gal-protein complexes. Furthermore, the conformation wherein the O6 atom is away from the aromatic residue is preferred for the exocyclic -CH 2 OH group in Galaromatic residue analog complexes. The implications of these results for saccharide binding in Gal-specific proteins and the possible role of the aromatic amino acid to ensure proper positioning and orientation of galactose in the binding site have been discussed.

Enzymatic Basis for N-Glycan Sialylation

“…The disaccharide in the ST3GAL1 structure is stabilized by extensive hydrogen bonding between Tyr-269 and the axial hydroxyls of the C4ЈOHs of the Gal and GalNAc and hydrogen bonds to the O6 of the Gal, interactions that take advantage of the down-facing axial hydroxyls of the disaccharide acceptor. For ST6GAL1, the interactions include hydrophobic stacking of Tyr-366 with the nonpolar side of the Gal residue and a network of hydrogen bonds to the Gal O2, O3, O4, and O6, a mode of hydrophobic stacking and hydrogen bonding that is common among Gal-specific binding proteins (91)(92)(93). The results are a series of interactions that are exquisitely complementary to the respective Gal residue orientations in the active sites, to position either the O3 (ST3GAL1) or O6 (ST6GAL1) acceptor appropriately for nucleophilic attack on the C2 position of the sugar donor.…”

Proper Fatty Acid Composition Rather than an Ionizable Lipid Amine Is Required for Full Transport Function of Lactose Permease from Escherichia coli

“…Protein-carbohydrate interactions typically also rely on aromatic stacking interactions of amino acid aromatic side chains with the sugar rings (41,42). The database of crystal structures with complexed carbohydrate moieties also reveals interactions between the carbohydrate CH groups and the -electron cloud of aromatic residues.…”

Glycolipid transfer proteins

“…Y207) to form 'cooperative' hydrogen bonds. The liganding interaction pattern, involving sugar stacking against an aromatic residue to enable formation of hydrogen bond tethers with peripheral sugar hydroxyls, observed in the all-α-helical conformation of GLTP is a conserved feature of other carbohydrate binding proteins, including all known galactose-specific binding proteins, all of which have α + β or all β conformational architectures [83][84][85][86].…”