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Transient hydrogen bonding in uniformly 13C,  15N labeled carbohydrates in water
Stockholm University, Faculty of Science, Department of Organic Chemistry.
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2012 (English)In: Biopolymers, ISSN 0006-3525, E-ISSN 1097-0282, Vol. 97, no 3, 145-154 p.Article in journal (Refereed) Published
Abstract [en]

We report NMR studies of transient hydrogen bonding in a polysaccharide (PS) dissolved in water without cosolvent at ambient temperature. The PS portion of the Escherichia coli O142 lipopolysaccharide is comprised of repeating pentasaccharide units of GalNAc (N-acetyl galactosamine), GlcNAc (N-acetyl glucosamine), and rhamnose in a 3:1:1 ratio, respectively. A 105-ns molecular dynamics (MD) simulation on one pentasaccharide repeat unit predicts transient inter-residue hydrogen bonds from the GalNAc NH groups in the PS. To investigate these predictions experimentally, the PS was uniformly 13C,15N enriched and the NH, carbonyl, C2, C4, and methyl resonances of the GalNAc and GlcNAc residues assigned using through-bond triple-resonance NMR experiments. Temperature dependence of amide NH chemical shifts and one-bond NH J couplings support that NH groups on two of the GalNAc residues are donors in transient hydrogen bonds. The remaining GalNAc and GlcNAc NHs do not appear to be donors from either temperature-dependent chemical shifts or one-bond NH J couplings. These results substantiate the presence of weak or partial hydrogen bonds in carbohydrates, and that MD simulations of repeating units in PSs provide insight into overall PS structure and dynamics.

Place, publisher, year, edition, pages
Wiley Periodicals, Inc. , 2012. Vol. 97, no 3, 145-154 p.
Keyword [en]
polysaccharides, carbohydrate NMR, oligosaccharide, isotopic labeling, molecular dynamics simulations, radial distribution function, hydrogen bonding
National Category
Organic Chemistry
URN: urn:nbn:se:su:diva-30113DOI: 10.1002/bip.21710ISI: 000298480400001PubMedID: 21858784OAI: diva2:241525
Available from: 2009-10-04 Created: 2009-10-04 Last updated: 2012-05-30Bibliographically approved
In thesis
1. Structure, dynamics and interactions of biomolecules: Investigations by NMR spectroscopy and computational methods
Open this publication in new window or tab >>Structure, dynamics and interactions of biomolecules: Investigations by NMR spectroscopy and computational methods
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In this thesis, the structure, dynamics and interactions of proteins and carbohydrates are investigated using mainly NMR spectroscopy and computer simulations.

Oligosaccharides representing a Salmonella O-antigen have been synthesized and their dynamic behavior and interaction with the bacteriophage P22 tail-spike protein have been studied by NMR spectroscopy, MD and docking simulations. A binding mechanism between the protein and the O-antigen has been proposed.

Transient hydrogen bonds have been defined and examined in an E. coli polysaccharide and in a pentasaccharide representing the repeating unit, using MD simulation and NMR spectroscopy.

Conformational dynamics of a trisaccharide representing the repeating unit of an A. salmonicida O-antigen have been investigated by MD simulations. The simulation together with relaxation matrix calculations reveals a conformational exchange on a ns timescale and explains an unusual NOE.

A fragment-based screening for inhibitors of the glycosyltransferase GTB acceptor site has been performed using NMR spectroscopy and SPR. IC50 values of the binding fragments are reported. Complex structures of the fragments and GTB have been proposed using docking simulations.

A fragment-based screening for inhibitors of the WaaG glycosyltransferase donor site has been performed using NMR spectroscopy and three compounds were selected. Structures of the WaaG-fragment complexes have been suggested from docking simulations. Binding of natural substrates and activity has also been investigated by NMR spectroscopy. MD simulations have been carried out on WaaG with and without bound donor substrate. The simulation revealed a conformational change upon substrate binding.

Interactions between HEWL and carbohydrate ligands have been investigated, using a combination of weak affinity chromatography, NMR spectroscopy and computer simulations. KDs of the ligands have been presented as well as the solution structures of two HEWL-disaccharide complexes.

Place, publisher, year, edition, pages
Stockholm: Department of Organic Chemistry, Stockholm University, 2009. 82 p.
NMR spectroscopy, MD simulation, carbohydrate synthesis, protein-ligand interaction, glycosyltransferase
National Category
Chemical Sciences
Research subject
Organic Chemistry
urn:nbn:se:su:diva-30120 (URN)978-91-7155-953-1 (ISBN)
Public defence
2009-11-13, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Submitted. Paper 4: Submitted. Paper 5: In progress. Paper 6: In progress. Paper 7: Manuscript.Available from: 2009-10-22 Created: 2009-10-04 Last updated: 2011-11-23Bibliographically approved

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