链激酶、纤溶酶与α2-抗纤溶酶之间反应的动力学

Kinetics of the reactions between streptokinase, plasmin and alpha 2-antiplasmin.

作者信息

Cederholm-Williams S A, De Cock F, Lijnen H R, Collen D

出版信息

Eur J Biochem. 1979 Oct;100(1):125-32. doi: 10.1111/j.1432-1033.1979.tb02040.x.

DOI:10.1111/j.1432-1033.1979.tb02040.x

Abstract

Streptokinase reacts very rapidly with human plasmin (rate constant 5.4 S 10(7) M-1 s-1) forming a 1:1 stoichiometric complex which has a dissociation constant of 5 X 10(-11) M. This plasmin-streptokinase complex is 10(5) times less reactive towards alpha 2-antiplasmin than plasmin, the inhibition rate constant being 1.4 X 10(2) M-1 s-1. The loss of reactivity of the streptokinase-plasmin complex towards alpha 2-antiplasmin is independent of the lysine binding sites in plasmin since low-Mr plasmin, which lacks these sites, and plasmin in which the sites have been blocked by 6-aminohexanoic acid, are both equally unreactive towards alpha 2-antiplasmin on reaction with streptokinase. The plasmin-streptokinase complex binds to Sepharose-lysine and Sepharose-fibrin monomer in the same fashion as free plasmin, showing that the lysine binding sites are fully exposed in the complex. Bovine plasmin is rapidly inhibited by human alpha 2-antiplasmin (k1 = 1.6 X 10(6) M-1 s-1) and similarly loses reactivity towards the inhibitor on complex formation with streptokinase (50% binding at 0.4 microM streptokinase).

摘要

链激酶与人纤溶酶反应非常迅速（速率常数为5.4×10⁷ M⁻¹ s⁻¹），形成1:1化学计量比的复合物，其解离常数为5×10⁻¹¹ M。这种纤溶酶 - 链激酶复合物对α₂ - 抗纤溶酶的反应性比纤溶酶低10⁵倍，抑制速率常数为1.4×10² M⁻¹ s⁻¹。链激酶 - 纤溶酶复合物对α₂ - 抗纤溶酶反应性的丧失与纤溶酶中的赖氨酸结合位点无关，因为缺乏这些位点的低分子量纤溶酶以及位点已被6 - 氨基己酸阻断的纤溶酶，在与链激酶反应后对α₂ - 抗纤溶酶的反应性均同样不高。纤溶酶 - 链激酶复合物与琼脂糖 - 赖氨酸和琼脂糖 - 纤维蛋白单体的结合方式与游离纤溶酶相同，表明赖氨酸结合位点在复合物中完全暴露。牛纤溶酶被人α₂ - 抗纤溶酶迅速抑制（k₁ = 1.6×10⁶ M⁻¹ s⁻¹），并且在与链激酶形成复合物时对抑制剂的反应性同样丧失（在0.4 μM链激酶时50%结合）。