title: Oligosaccharides implicated in recognition are predicted to have relatively ordered structures.
abstract: Fucosylated O- and N-linked glycans are essential recognition molecules in plants and animals. To understand how they impart their functions, through interactions with proteins, requires a detailed analysis of structure and dynamics, but this is presently lacking. In this study, the three-dimensional structure and dynamics of three fucosylated oligosaccharides are investigated using a combination of high field (800 MHz) nuclear magnetic resonance and long (50 ns) molecular dynamics simulations in explicit water. Predictions from dynamics simulations were in agreement with nuclear Overhauser cross-peak intensities. Similarly, a theory of weak alignment in neutral media resulted in reasonable predictions of residual dipolar couplings for the trisaccharide fucosyllactose. However, for larger penta- and hexasaccharides (LNF-1 and LND-1), the anisotropic component of the alignment was underestimated, attributed to shape irregularities of the fucosyl branches on an otherwise linear core, being more pronounced in a singly branched than a doubly branched oligosaccharide. Simulations, confirmed by experiment, predicted fucosylated molecules that are restricted to librations about a single average conformation. This restriction is partly due to microscopic water interactions, which act to stabilize intramolecular hydrogen bonds and maintain tight and ordered conformations; a view not forthcoming from simpler, nonaqueous simulations. Such a conclusion is crucial for understanding how these molecules interact with proteins and impart their recognition properties.
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom. Andrew.Almond@bioch.ox.ac.uk
authors.forename: Andrew
authors.initials: A
authors.lastname: Almond
authors.forename: Bent O
authors.initials: BO
authors.lastname: Petersen
authors.forename: Jens Ø
authors.initials: JØ
authors.lastname: Duus
mesh_terms: D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D003198:Computer Simulation; D005643:Fucose / Q000737:chemistry; D005690:Galactose / Q000737:chemistry; D005947:Glucose / Q000737:chemistry; D006860:Hydrogen Bonding; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D009844:Oligosaccharides / Q000737:chemistry*; D011237:Predictive Value of Tests; D012996:Solutions; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014312:Trisaccharides / Q000737:chemistry
chemical_list: D009844:Oligosaccharides; D012996:Solutions; D014312:Trisaccharides; D005643:Fucose; C045442:lacto-N-fucopentaose I; D005947:Glucose; D005690:Galactose