An unusual antithrombin-binding heparin octasaccharide with an additional 3-O-sulfated glucosamine in the active pentasaccharide sequence.

Content Provider	Semantic Scholar
Author	Guerrini, Marco Elli, Stefano Mourier, Pierre A. J. Rudd, Timothy R. Gaudesi, Davide Casu, Benito Boudier, Christian Torri, Giangiacomo Viskov, Christian
Copyright Year	2013
Abstract	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-low-molecular-mass heparin semuloparin, in which both glucosamine residues of the pentasaccharide moiety located at the non-reducing 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.
File Format	PDF HTM / HTML
DOI	10.1042/BJ20121309
PubMed reference number	23083208
Journal	Medline
Volume Number	449
Issue Number	2
Alternate Webpage(s)	http://www.biochemj.org/content/ppbiochemj/449/2/343.full.pdf
Alternate Webpage(s)	https://doi.org/10.1042/BJ20121309
Journal	The Biochemical journal
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article