| Autor: |
Guido Tans, Anton J. G. Horrevoets, A. Smilde, A.J. van Zonneveld, H. Pannekoek |
| Rok vydání: |
1993 |
| Předmět: |
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| Zdroj: |
Journal of Biological Chemistry. 268:779-782 |
| ISSN: |
0021-9258 |
| DOI: |
10.1016/s0021-9258(18)54001-1 |
| Popis: |
The importance of a specific variable region in different serine proteases for the interaction with plasminogen activator inhibitor 1 (PAI-1) is studied. To that end, we have constructed a thrombin substitution variant, thrombin-VR1, in which the entire variable region 1 (VR1) of the protease domain (Phe-34 to Leu-40) has been replaced by the corresponding sequence (Phe-294 to Phe-305) of tissue-type plasminogen activator. The substitution resulted in a 2000-fold increase of the second-order rate constant of inhibition by PAI-1 (k2 = 2.2 x 10(6) M-1 s-1) as compared to alpha-thrombin (k2 = 1.1 x 10(3) M-1 s-1). Inhibition of thrombin-VR1 by PAI-1 is mediated by the formation of SDS-stable, enzyme-inhibitor complexes. The substitution did not affect the rate constant of inhibition by antithrombin III, whereas clotting efficiency and the rate of inhibition by heparin cofactor II were decreased 3-fold. These results demonstrate the importance and specificity of the protease domain VR1 region for the interaction of PAI-1 with its target proteases. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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