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

The geometries of the contacts between monosaccharides and aromatic rings of amino adds 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/pi interactions and 859 of them (45%) without CH/pi interactions. We showed that only the carbohydrate/aromatic contacts with CH/pi interactions are preferentially parallel and enable sliding in the plane parallel to aromatic ring. The calculated interaction energies in systems with CH/pi interactions are in the range from -1.7 kcal/mol to -6.8 kcal/mol, while in the systems without CH/pi interactions are in the range -0.2 to -32 kcal/mol. Hence, the binding that does not include CH/pi 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/pi 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. (C) 2020 Published by Elsevier B.V.