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1: FEBS Lett. 2002 Jul 3;522(1-3):147-50.Click here to read Links

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

Hayakawa Y, Hirashima Y, Kurimoto M, Hayashi N, Hamada H, Kuwayama N, Endo S.

Department of Neurosurgery, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Japan. hayakawa@ms.toyama-mpu.ac.jp

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.

PMID: 12095635 [PubMed - indexed for MEDLINE]

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