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Binding of heparin or dermatan sulfate to thrombin is essential for the sulfated polysaccharide‐accelerated inhibition of thrombin by heparin cofactor II
Author(s) -
Yamagishi Ryoichi,
Koide Takehiko,
Sakuragawa Nobuo
Publication year - 1987
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(87)81140-7
Subject(s) - heparin cofactor ii , dermatan sulfate , thrombin , chemistry , heparin , biochemistry , sulfation , cofactor , discovery and development of direct thrombin inhibitors , heparan sulfate , antithrombin , enzyme , platelet , immunology , biology
Heparin cofactor II (HC II) and thrombin were chemically modified with pyridoxal 5′‐phosphate, and their effects on the inhibition of thrombin by HC II in the presence of heparin or dermatan sulfate were studied. The inhibition of thrombin by HC II was enhanced about 7000‐fold in the presence of heparin or dermatan sulfate. However, this enhancement by heparin dwindled to 110‐ and 9.6‐fold when the modified HC II and the modified thrombin, respectively, were substituted for native proteins. Essentially identical results were obtained from the experiments using dermatan sulfate. These results indicate that the binding of heparin or dermatan sulfate to both thrombin and HC II is required for the sulfated polysaccharide‐dependent acceleration of the thrombin inhibition by HC II, and the binding to thrombin is more essential for the reaction.