Oligosaccharides implicated in recognition are predicted to have relatively ordered structures

A. Almond, Bent O. Petersen, Jens Øllgaard Duus

Research output: Contribution to journalJournal articleResearchpeer-review

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.
Original languageEnglish
JournalBiochemistry
Volume43
Issue number19
Pages (from-to)5853-5863
Number of pages11
ISSN0006-2960
DOIs
Publication statusPublished - 2004
Externally publishedYes

Keywords

  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Computer Simulation
  • Fucose
  • Galactose
  • Glucose
  • Hydrogen Bonding
  • Nuclear Magnetic Resonance, Biomolecular
  • Oligosaccharides
  • Predictive Value of Tests
  • Solutions
  • Stereoisomerism
  • Structure-Activity Relationship
  • Thermodynamics
  • Trisaccharides
  • 3713-31-3 Fucose
  • 7578-25-8 lacto-N-fucopentaose I
  • IY9XDZ35W2 Glucose
  • X2RN3Q8DNE Galactose
  • Computer simulation
  • Conformations
  • Hydrogen bonds
  • Molecular dynamics
  • Nitrogen
  • Oxygen
  • Plants (botany)
  • Water
  • Biochemistry
  • fusosyllactose
  • glycan
  • oligosaccharide
  • pentasaccharide
  • protein
  • trisaccharide
  • unclassified drug
  • water
  • animal
  • anisotropy
  • article
  • carbohydrate analysis
  • conformation
  • hydrogen bond
  • molecular dynamics
  • molecular recognition
  • nuclear magnetic resonance
  • nuclear Overhauser effect
  • plant
  • prediction
  • priority journal
  • protein interaction
  • simulation
  • structure analysis
  • Animalia
  • Dipolar couplings
  • Ordered structures
  • X
  • BIOCHEMISTRY
  • RESIDUAL DIPOLAR COUPLINGS
  • MOLECULAR-DYNAMICS SIMULATIONS
  • BLOOD-GROUP OLIGOSACCHARIDES
  • CONFORMATIONAL-ANALYSIS
  • AQUEOUS-SOLUTION
  • GROUP-A
  • NMR-SPECTROSCOPY
  • N-GLYCANS
  • LEWIS-X
  • CONSTANTS
  • hydrogen bonding
  • microscopic water interactions
  • fucosylated N-linked glycans
  • fucosylated O-linked glycans
  • oligosaccharides ordered structures
  • 10060, Biochemistry studies - General
  • 10068, Biochemistry studies - Carbohydrates
  • Biochemistry and Molecular Biophysics
  • OLIGOSACCHARIDES

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