The interaction of glycosaminoglycans with heparin cofactor II: structure and activity of a high-affinity dermatan sulfate hexasaccharide.
The binding sites for dermatan sulfate and heparin in HCII overlap but are not identical. This may explain the observation that HCII binds non-specifically to heparin oligosaccharides but preferentially binds to a minor hexasaccharide isolated from dermatan sulfate having the structure shown in Fig. 4B. The tissue distribution of dermatan sulfate molecules containing the high-affinity HCII binding site may regulate HCII activity in vivo. Finally, in the presence of dermatan sulfate or heparin, the N-terminal acidic domain of HCII may interact with the hirudin-binding site of thrombin to produce maximal stimulation of the thrombin-HCII reaction.
Tollefsen
D M
DM
Department of Internal Medicine, Washington University, St. Louis, Missouri 63110.
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002240:Carbohydrate Sequence; D003871:Dermatan Sulfate / Q000737:chemistry / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D015844:Heparin Cofactor II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008956:Models, Chemical; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D013917:Thrombin / Q000037:antagonists & inhibitors
D006025:Glycosaminoglycans; D009844:Oligosaccharides; D003871:Dermatan Sulfate; D015844:Heparin Cofactor II; D013917:Thrombin