Contribution of basic residues of the A helix of heparin cofactor II to heparin‐ or dermatan sulfate‐mediated thrombin inhibition

FEBS Letters

Hamada, Hideo¹  Endo, Shunro¹  Kuwayama, Naoya¹  Hayashi, Nakamasa¹  Hirashima, Yutaka¹  Hayakawa, Yumiko¹  Kurimoto, Masanori¹ 

[1] Department of Neurosurgery, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan

关键词: Serpin;    Heparin cofactor II;    Heparin;    Dermatan sulfate;    Thrombin;    HCII;    heparin cofactor II;    rHCII;    recombinant heparin cofactor II;    serpin;    serine protease inhibitor;    AT;    antithrombin;    GAG;    glycosaminoglycan;   

DOI  :  10.1016/S0014-5793(02)02930-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 (Lys¹⁰¹ and Arg¹⁰⁶) are necessary for heparin- or dermatan sulfate-accelerated thrombin inhibition.

【 授权许可】

Unknown