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
• databáze proteinů MeSH
• konformace proteinů MeSH
• krystalografie rentgenová MeSH
• lektiny chemie   metabolismus   MeSH
• metabolismus sacharidů * MeSH
• tryptofan chemie   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• lectin, Aleuria aurantia MeSH Prohlížeč
• lektiny MeSH
• tryptofan 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.

• Klíčová slova
• CH/π interactions, carbohydrate-protein interactions, interaction energy, lectins, non-canonical hydrogen bond,
• MeSH
• lektiny chemie   metabolismus   MeSH
• molekulární modely MeSH
• sacharidy chemie   MeSH
• vazba proteinů MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• lektiny MeSH
• sacharidy 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
• aminokyseliny aromatické chemie   genetika   metabolismus   MeSH
• bakteriální proteiny chemie   genetika   metabolismus   MeSH
• fukosa chemie   metabolismus   MeSH
• konformace proteinů MeSH
• konformace sacharidů MeSH
• krystalografie rentgenová MeSH
• lektiny chemie   genetika   metabolismus   MeSH
• molekulární modely * MeSH
• mutace MeSH
• proteiny chemie   genetika   metabolismus   MeSH
• Ralstonia solanacearum genetika   metabolismus   MeSH
• sacharidy chemie   MeSH
• sekundární struktura proteinů MeSH
• terciární struktura proteinů MeSH
• termodynamika MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokyseliny aromatické MeSH
• bakteriální proteiny MeSH
• fukosa MeSH
• lektiny MeSH
• proteiny MeSH
• sacharidy MeSH