2KQO

A 3D-structural model of unsulphated chondroitin from high-field NMR: 4-sulphation has little effect on backbone conformation

Summary for 2KQO

• Entry DOI: 10.2210/pdb2kqo/pdb
• Descriptor: beta-D-glucopyranuronic acid-(1-3)-2-acetamido-2-deoxy-beta-D-galactopyranose-(1-4)-beta-D-glucopyranuronic acid-(1-3)-2-acetamido-2-deoxy-beta-D-galactopyranose-(1-4)-beta-D-glucopyranuronic acid-(1-3)-2-acetamido-2-deoxy-beta-D-galactopyranose (1 entity in total)
• Functional Keywords: unsulphated chondroitin, conformation, n-acetyl-d-galactosamine, d-glucuronic acid, explicit solvent molecular dynamics simulation, extracellular matrix, glycosaminoglycan, carbohydrate
• Total formula weight: 1155.96

Authors

Sattelle, B.M.,Shakeri, J.,Roberts, I.S.,Almond, A. (deposition date: 2009-11-12, release date: 2009-12-01, Last modification date: 2024-05-01)

Primary citation

Sattelle, B.M.,Shakeri, J.,Roberts, I.S.,Almond, A.
A 3D-structural model of unsulfated chondroitin from high-field NMR: 4-sulfation has little effect on backbone conformation.
Carbohydr.Res., 345:291-302, 2010

PubMed Abstract: The glycosaminoglycan chondroitin sulfate is essential in human health and disease but exactly how sulfation dictates its 3D-structure at the atomic level is unclear. To address this, we have purified homogenous oligosaccharides of unsulfated chondroitin (with and without (15)N-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 O5 atoms across the beta(1-->3) glycosidic linkage. The unsulfated chondroitin bond geometry differs slightly from hyaluronan by 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.

PubMed: 20022001
DOI: 10.1016/j.carres.2009.11.013

Experimental method

SOLUTION NMR