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

• Published in: International journal of biological macromolecules Vol. 157; pp. 1 - 9
• Main Authors: Stanković, Ivana M., Blagojević Filipović, Jelena P., Zarić, Snežana D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.08.2020
• Subjects: Amino Acids, Aromatic - chemistry; Amino Acids, Aromatic - metabolism; Aromatic amino acids; Carbohydrate Metabolism; Carbohydrates; Carbohydrates - chemistry; CH/π interactions; Databases, Protein; Monosaccharides - chemistry; Monosaccharides - metabolism; Proteins - chemistry; Proteins - metabolism; Quantum Theory; Stacking interactions; Carbohydrates; RSL; Stacking interactions; CCSD(T); VMD; CH/π interactions; MP2; PDB; NMR; CBS; MD; Aromatic amino acids; BSSE
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2020.03.251

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. •The carbohydrate/aromatic contacts with and without CH/π interactions are found in the PDB structures with similar frequency.•The contacts with CH/π are preferentially parallel and sliding in the ring plane, in contrast with those without CH/π.•Proteins arrange more or less evenly their aromatic rings onto every second unit of carbohydrate oligomers.•The calculated energies for the contacts without CH/π are significant (up to -3.2 kcal/mol) and should not be neglected.