Protein-carbohydrate interactions are very often mediated by the stacking CH-π interactions involving the side chains of aromatic amino acids such as tryptophan (Trp), tyrosine (Tyr) or phenylalanine (Phe). Especially suitable for stacking is the Trp residue. Analysis of the PDB database shows Trp stacking for 265 carbohydrate or carbohydrate like ligands in 5 208 Trp containing motives. An appropriate model system to study such an interaction is the AAL lectin family where the stacking interactions play a crucial role and are thought to be a driving force for carbohydrate binding. In this study we present data showing a novel finding in the stacking interaction of the AAL Trp side chain with the carbohydrate. High resolution X-ray structure of the AAL lectin from Aleuria aurantia with α-methyl-l-fucoside ligand shows two possible Trp side chain conformations with the same occupation in electron density. The in silico data shows that the conformation of the Trp side chain does not influence the interaction energy despite the fact that each conformation creates interactions with different carbohydrate CH groups. Moreover, the PDB data search shows that the conformations are almost equally distributed across all Trp-carbohydrate complexes, which would suggest no substantial preference for one conformation over another.

• MeSH
• Databases, Protein MeSH
• Protein Conformation MeSH
• Crystallography, X-Ray MeSH
• Lectins chemistry   metabolism   MeSH
• Carbohydrate Metabolism * MeSH
• Tryptophan chemistry   metabolism   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• lectin, Aleuria aurantia MeSH Browser
• Lectins MeSH
• Tryptophan MeSH

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,
• MeSH
• Lectins chemistry   metabolism   MeSH
• Models, Molecular MeSH
• Carbohydrates chemistry   MeSH
• Protein Binding MeSH
• Hydrogen Bonding MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Lectins MeSH
• Carbohydrates MeSH

Carbohydrate-receptor interactions are an integral part of biological events. They play an important role in many cellular processes, such as cell-cell adhesion, cell differentiation and in-cell signaling. Carbohydrates can interact with a receptor by using several types of intermolecular interactions. One of the most important is the interaction of a carbohydrate's apolar part with aromatic amino acid residues, known as dispersion interaction or CH/π interaction. In the study presented here, we attempted for the first time to quantify how the CH/π interaction contributes to a more general carbohydrate-protein interaction. We used a combined experimental approach, creating single and double point mutants with high level computational methods, and applied both to Ralstonia solanacearum (RSL) lectin complexes with α-L-Me-fucoside. Experimentally measured binding affinities were compared with computed carbohydrate-aromatic amino acid residue interaction energies. Experimental binding affinities for the RSL wild type, phenylalanine and alanine mutants were -8.5, -7.1 and -4.1 kcal x mol(-1), respectively. These affinities agree with the computed dispersion interaction energy between carbohydrate and aromatic amino acid residues for RSL wild type and phenylalanine, with values -8.8, -7.9 kcal x mol(-1), excluding the alanine mutant where the interaction energy was -0.9 kcal x mol(-1). Molecular dynamics simulations show that discrepancy can be caused by creation of a new hydrogen bond between the α-L-Me-fucoside and RSL. Observed results suggest that in this and similar cases the carbohydrate-receptor interaction can be driven mainly by a dispersion interaction.

• MeSH
• Amino Acids, Aromatic chemistry   genetics   metabolism   MeSH
• Bacterial Proteins chemistry   genetics   metabolism   MeSH
• Fucose chemistry   metabolism   MeSH
• Protein Conformation MeSH
• Carbohydrate Conformation MeSH
• Crystallography, X-Ray MeSH
• Lectins chemistry   genetics   metabolism   MeSH
• Models, Molecular * MeSH
• Mutation MeSH
• Proteins chemistry   genetics   metabolism   MeSH
• Ralstonia solanacearum genetics   metabolism   MeSH
• Carbohydrates chemistry   MeSH
• Protein Structure, Secondary MeSH
• Protein Structure, Tertiary MeSH
• Thermodynamics MeSH
• Protein Binding MeSH
• Binding Sites MeSH
• Hydrogen Bonding MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Amino Acids, Aromatic MeSH
• Bacterial Proteins MeSH
• Fucose MeSH
• Lectins MeSH
• Proteins MeSH
• Carbohydrates MeSH