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Contribution of basic residues of the A helix of heparin cofactor II to heparin‐ or dermatan sulfate‐mediated thrombin inhibition
Author(s) -
Hayakawa Yumiko,
Hirashima Yutaka,
Kurimoto Masanori,
Hayashi Nakamasa,
Hamada Hideo,
Kuwayama Naoya,
Endo Shunro
Publication year - 2002
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/s0014-5793(02)02930-7
Subject(s) - heparin cofactor ii , dermatan sulfate , thrombin , chemistry , heparin , biochemistry , antithrombins , cofactor , heparan sulfate , enzyme , antithrombin , biology , platelet , immunology
Inhibition of thrombin by heparin cofactor II (HCII) is accelerated 1000‐fold by heparin or dermatan sulfate. To investigate the contribution of basic residues of the A helix of HCII to this activation, we constructed amino acid substitutions (K101Q, R103L, and R106L) by site‐directed mutagenesis. K101Q greatly reduced heparin cofactor activity and required a more than 10‐fold higher concentration of dermatan sulfate to accelerate thrombin inhibition compared with wild‐type recombinant HCII. Thrombin inhibition by R106L was not significantly stimulated by dermatan sulfate. These results provide evidence that basic residues of the A helix of HCII (Lys 101 and Arg 106 ) are necessary for heparin‐ or dermatan sulfate‐accelerated thrombin inhibition.