| Autor: |
GUERRINI, Marco, ELLI, Stefano, MOURIER, Pierre, RUDD, Timothy R., GAUDESI, Davide, CASU, Benito, BOUDIER, Christian, TORRI, Giangiacomo, VISKOV, Christian |
| Předmět: |
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| Zdroj: |
Biochemical Journal; 1/15/2013, Vol. 449 Issue 2, following p343-351, 14p |
| Abstrakt: |
The 3-O-sulfation of N-sulfated glucosamine is the last event in the biosynthesis of heparin/heparan sulfate, giving rise to the antithrombin-binding pentasaccharide sequence AGA*IA, which is largely associated with the antithrombotic activity of these molecules. The aim of the present study was the structural and biochemical characterization of a previously unreported AGA*IA*-containing octasaccharide isolated from the very-lowmolecular- mass heparin semuloparin, in which both glucosamine residues of the pentasaccharide moiety located at the nonreducing end bear 3-O-sulfate groups. Two-dimensional and STD (saturation transfer difference) NMR experiments clearly confirmed its structure and identified its ligand epitope binding to antithrombin. The molecular conformation of the octasaccharide- antithrombin complex has been determined by NMR experiments and docking/energy minimization. The presence of the second 3-O-sulfated glucosamine in the octasaccharide induced more than one order of magnitude increase in affinity to antithrombin compared to the pentasaccharide AGA*IA. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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