Insights into the Role of the Aromatic Residue in Galactose-Binding Sites:  MP2/6-311G++** Study on Galactose− and Glucose−Aromatic Residue Analogue Complexes

Abstract

The presence of an aromatic residue (Trp, Phe, Tyr) facing the nonpolar face of galactose is a common feature of galactose-specific lectins. The interactions such as those between the C-H groups of galactose and the pi-electron cloud of aromatic residues have been characterized as weak hydrogen bonds between soft acids and soft bases, largely governed by dispersive and charge transfer interactions. An analysis of the binding sites of several galactose-specific lectins revealed that the spatial position-orientation of galactose relative to the binding site aromatic residue varies substantially. The effect of variations in position-orientations of galactose on the interaction energies of galactose-aromatic residue complexes has not been determined so far. In view of this, MP2/6-311G++** calculations were performed on galactose- and glucose-aromatic residue analogue complexes in eight position-orientations. The results show that the strength of the C-H...pi interactions in galactose-aromatic residue complexes is comparable to that of a hydrogen bond. Rather than the type of aromatic residue, the position-orientation of the saccharide appears to be more critical in determining the strength of their interactions. Earlier studies have found the binding site aromatic residue to be critical, but its role was not clear. This study shows that the aromatic residue is important for discriminating galactose from glucose, in addition to its contribution to binding energy.

Aromatic interactions at the catalytic subsite of sucrose phosphorylase: Their roles in enzymatic glucosyl transfer probed with Phe52 → Ala and Phe52 → Asn mutants

“…Fructose was constant at 100 mM. 4 Fructose was varied at 12 levels between 1 and 200 mM. Glc1P was constant at 100 mM.…”

“…Its proposed role in catalysis is to aid in the conformational itinerary of the glycopyranoside upon moving from the ground state (e.g. 4 C 1 chair) to the oxocarbenium ion-like transition state (e.g. 4 H 3 half-chair).…”

“…4 C 1 chair) to the oxocarbenium ion-like transition state (e.g. 4 H 3 half-chair). Non-polar contacts with the hydrophobic C 4 -C 5 -hydroxymethyl moiety of the glycopyranoside that become tightened in the transition state are believed to be the source of the catalytic facilitation provided.…”

Docking Studies Show That D-Glucose and Quercetin Slide through the Transporter GLUT1

“…2C, Table 3). The preference for ␤-D-galactose and ␤-D-glucose over ␣-anomers for aromatic residues (Table 2) suggests that the ␣ axial C1 OH of the pyranose ring increases the separation distance between the axial C-Hs and the -electrons of the aromatic side chains and thereby reduces its affinity for the aromatic slipway (43,44).…”

“…2B) and the higher frequency of binding of planar ␤-D-hexose anomers than ␣-anomers (Table 2) by forming -bonds with the aromatic residues in the pore (43,44). Further evidence for this awaits detailed molecular dynamic simulations.…”