CH/π Interactions in Carbohydrate Recognition

Abstract

Many carbohydrate-binding proteins contain aromatic amino acid residues in their binding sites. These residues interact with carbohydrates in a stacking geometry via CH/π interactions. These interactions can be found in carbohydrate-binding proteins, including lectins, enzymes and carbohydrate transporters. Besides this, many non-protein aromatic molecules (natural as well as artificial) can bind saccharides using these interactions. Recent computational and experimental studies have shown that carbohydrate-aromatic CH/π interactions are dispersion interactions, tuned by electrostatics and partially stabilized by a hydrophobic effect in solvated systems.

Keywords: CH/π interactions; carbohydrate-protein interactions; interaction energy; lectins; non-canonical hydrogen bond.

Figure 1

Comparison of β-galactosidases monomers from E. coli (A, with bound lactose, PDB ID: 1JZ8) and Arthrobacter sp. C2-2 (B, PDB ID: 1YQ2).

Figure 2

Prevalent geometries of carbohydrate–aromatic CH/π interactions: (A) β-d-glucopyranose can interact via both faces (only the A face is available for α-d-glucopyranose); (B) α- or β-d-galacto- or d-fucopyranose interacts via hydrogens on atoms C3, C4, C5 and C6 (a mirror assembly is typical for l-fucopyranose); (C) β-d-mannopyranose interacts via hydrogen atoms on C1, C2 and C3.

Figure 3

Examples of carbohydrate–aromatic complexes. (A) Cellulomonas fimi carbohydrate binding module CMB4 with (β-d-Glcp)₅ (PDB ID: 1GU3); (B) Clostridium thermocellum endoglucanase CelA with (β-d-Glcp)₆ (PDB ID: 1KWF); (C) “Greasy slide” of E. coli LamB maltoporin with two maltose molecules (PDB ID: 1MPM, residue W*74 belongs to another protein chain); (D) “Sugar tongs” in barley α-amylase (Y105 and Y52 form the active site; Y380 forms the “sugar tongs” site).

Figure 4

Examples of artificial carbohydrate–aromatic complexes: (A) An artificial carbohydrate receptor with ligand cellobiose (illustrative 3D structure generated by Avogadro [25]); (B) Schematic view of carbon nanotube solubilization by amylose; (C) Writing by pencil on a paper (top) and erasing it by a pencil eraser (bottom).