Stacking Interactions between Carbohydrate and Protein Quantified by Combination of Theoretical and Experimental Methods

Investor logo
Investor logo
Investor logo
Investor logo

Warning

This publication doesn't include Faculty of Economics and Administration. It includes Central European Institute of Technology. Official publication website can be found on muni.cz.
Authors

WIMMEROVÁ Michaela KOZMON Stanislav NEČASOVÁ Ivona MISHRA Sushil Kumar KOMÁREK Jan KOČA Jaroslav

Year of publication 2012
Type Article in Periodical
Magazine / Source Plos One
MU Faculty or unit

Central European Institute of Technology

Citation
Web http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0046032
Doi http://dx.doi.org/10.1371/journal.pone.0046032
Field Biochemistry
Keywords SMALL MOLECULAR-INTERACTIONS; DENSITY-FUNCTIONAL THEORY; SEPARATE TOTAL ENERGIES; INTERACTIONS AB-INITIO; DOT-PI-INTERACTIONS; O HYDROGEN-BONDS; AROMATIC INTERACTIONS; RALSTONIA-SOLANACEARUM; STRUCTURAL BASIS; EXCHANGE-ENERGY
Attached files
Description 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/pi interaction. In the study presented here, we attempted for the first time to quantify how the CH/pi 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 alpha-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.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.mol(-1), excluding the alanine mutant where the interaction energy was -0.9 kcal.mol(-1). Molecular dynamics simulations show that discrepancy can be caused by creation of a new hydrogen bond between the alpha-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.
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.