Journal
CARBOHYDRATE RESEARCH
Volume 345, Issue 2, Pages 291-302Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carres.2009.11.013
Keywords
Chondroitin sulfate; N-15-isotope incorporation; Conformation; NMR; K4 polysaccharide
Funding
- Wellcome Trust [075489]
- Biotechnology and Biological Sciences Research Council [BBS/B/09627] Funding Source: researchfish
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The glycosaminoglycan chondroitin sulfate is essential in human health and disease but exactly how sulfation dictates its 3D-strucutre at the atomic level is unclear. To address this, we have purified homogenous oligosaccharides of unsulfated chondroitin (with and without N-15-enrichment) and analysed them by high-field NMR to make a comparison published chondroitin sulfate and hyaluronan 3D-structures. The result is the first full assignment of the tetrasaccharide and an experimental 3D-model of the hexasaccharide (PDB code 2KQO). In common with hyaluronan, we confirm that the amide proton is not involved in strong, persistent inter-residue hydrogen bonds. However, in contrast to hyaluronan, a hydrogen bond is not inferred between the hexosamine OH-4 and the glucuronic acid 05 atoms across the beta(1 -> 3) glycosidic linkage. The unsulfated chondroitin bond geometry differs slightly from hyaluronan y rotation about the beta(1 -> 3) psi dihedral (as previously predicted by simulation), while the beta(1 -> 4) linkage is unaffected. Furthermore, comparison shows that this glycosidic linkage geometry is similar in chondroitin-4-sulfate. We therefore hypothesise that both hexosamine OH-4 and OH-6 atoms are solvent exposed in chondroitin, explaining why it is amenable to sulfation and hyaluronan is not, and also that 4-sulfation has little effect on backbone conformation. Our conclusions exemplify the value of the 3D-model presented here and progress our understanding of glycosaminoglycan molecular properties. (C) 2009 Elsevier Ltd. All rights reserved.
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