AsianScientist (Sep. 16, 2014) – A research group lead by Professor Koichi Kato of the Institute for Molecular Science, National Institutes of Natural Sciences has developed a method for quantitatively describing the dynamic behaviors of complicated sugar chains in solution at atomic resolution. This study has just been published in Angewandte Chemie International Edition.
The sugar chains are flexible accessories decorating the surface of proteins. These variable accessories mediate protein-protein communication and even determine the fates of the protein. In other words, the sugar chains serve as transformable “code” that governs the protein’s action in our body. For example, particular sugar chains modifying lipids on cell surfaces offer acceptor sites for viral infections and trigger conformational changes of proteins involved in neurodegenerative disorders including Alzheimer’s disease.
Understanding the sugar code would not only improve our understanding the molecular mechanisms behind a variety of biological processes but also facilitate the design of new drugs targeting these processes. NMR spectroscopy is one of the most promising experimental approaches for conformational analyses of the sugar chains because of its ability to determine geometrical arrangements of the atoms constituting biomolecules in solution.
However, if a biomolecule undergoes rapid motion as in the case of the sugar chains, NMR can only provide information averaged over all its possible conformational snapshots. In contrast, a molecular dynamics simulation can provide a movie that describes the dynamic behaviors of sugar chains, but the simulation results need to be experimentally validated.
Prof. Kato’s research group combined these two complementary approaches, thereby successfully capturing distinct conformational snapshots of two very similar sugar chains in dynamic motion. They used genetically engineered yeast cells to produce stable isotope labelled oligosaccharides in sufficient quantities. Next, a paramagnetic probe was introduced specifically at one end of the oligosaccharides in order to obtain atomic-distance information. The labelled oligosaccarides where then visualized using the high-field NMR spectrometers and the supercomputer facility operated by the Institute for Molecular Science.
As Professor Kato notes, “This success enables us quantitative and highly sensitive characterization of minor but biologically relevant conformational species of sugar chains and will open the door for observing the dynamic behavior of flexible biomolecules as potential drug targets.”
The article can be found at: Yamaguchi et al. (2014) Exploration of Conformational Spaces of High-Mannose-Type Oligosaccharides by an NMR-Validated Simulation.
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Source: National Institutes of Natural Sciences; Photo: Koichi Kato/Institute for Molecular Science.
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