Carbohydrate – Protein aromatic ring interactions beyond CH/π interactions: A Protein Data Bank survey and quantum chemical calculations

Abstract

The geometries of the contacts between monosaccharides and aromatic rings of amino acids found in X-ray crystallography structures, in the Protein Data Bank (PDB), were analyzed, while the energies of the interactions were calculated using quantum chemical method. We found 1913 sugar/aromatic ring contacts, 1054 of them (55%) with CH/π interactions and 859 of them (45%) without CH/π interactions. We showed that only the carbohydrate/aromatic contacts with CH/π interactions are preferentially parallel and enable sliding in the plane parallel to aromatic ring. The calculated interaction energies in systems with CH/π interactions are in the range from −1.7 kcal/mol to −6.8 kcal/mol, while in the systems without CH/π interactions are in the range −0.2 to −3.2 kcal/mol. Hence, the binding that does not include CH/π interactions, can also be important for aromatic amino acid and carbohydrate binding processes, since some of these interactions can be as strong as the CH/π interactions. At the same time, these interactions can be weak enough to enable releasing of small carbohydrate fragments after the enzymatic reaction. The analysis of the protein-substrate patterns showed that every second or third carbohydrate unit in long substrates stacks with protein aromatic amino acids.