A unique trisaccharide sequence in heparin mediates the early step of antithrombin III activation

Maurice Petitou, Térésa Barzu, Jean-Pascal Herault, Jean-Marc Herbert
1997 Glycobiology  
Spectrofluorimetry experiments using synthetic trisaccharides indicate that in compounds that display affinity for antithrombin El (AT-III), a unique trisaccharide sequence plays the key role in the eariy recognition, and the first step of AT-IU activation. Added to previous observations, these new results suggest that the two-step binding mechanism previously proposed (Olson et al, J. BioL Chem., 1981,256, 11073-11079) might involve, in the first place, a confonnational change of the protein,
more » ... nduced by the trisasaccharide -»4)-0-(6-0-suIfo-2-sulfoamino-2-deoxy-a-D-glucopyranosyl)-(l-»4)-0-(3-D-glucopyranosyluronic acid)-(l->4)-O-(3,6-di-O-sulfo-2-suIfoamino-2-deoxy-a-Dglucopyranosyl)-(l->, then would follow the fitting which ends in the locked complex. These observations support the new paradigm invoking specific oligosaccharide sequences in selective interactions of glycosaminoglycans and proteins. Key words: antithrombin/coagulation/glycosaminoglycan/ heparin/interaction ARG 46 ARG 47 LYS 136 LYS 133 ARG 132 ARG 129 LYS 125 Helix D
doi:10.1093/glycob/7.3.323-e pmid:9147040 fatcat:6kmutvzsyjhwfhrz36efoxzk7q