Strukova S M, Dugina T N, Kireeva E G, Brodskiĭ L I, Kogan A E, Ashmarin I P
Vestn Akad Med Nauk SSSR. 1991(10):28-33.
The structural and functional features of thrombin are under discussion: combination of restricted specificity and a central regulatory role in hemostasis. Thrombin specificity is mainly connected with special regions of the enzyme molecule--an additional recognition binding site for high molecular substrates. One can consider the additional site of thrombin as a kind of the allosteric centre changing thrombin-catalyzed functions at binding with modulator. Specific site of substrate (inhibitor or receptor) is used in the role of modulator. A computer search of that modulator was fulfilled by means of the program DOTHELIX. The peptides thymosin I and substance P which have regions similar to those of hirudin were shown to inhibit thrombin activity. The kinetic data point to the noncompetitive type of inhibition. The data on the high reactivity of the thrombin-activated protein C system confirm the idea of protein C to be the first defensive mechanism when thrombin is generated in blood and interacts with thrombomodulin.
其特异性受限并在止血过程中起核心调节作用。凝血酶的特异性主要与酶分子的特殊区域相关——这是一个用于识别高分子底物的额外结合位点。可以将凝血酶的这个额外位点视为一种变构中心，在与调节剂结合时会改变凝血酶催化的功能。底物（抑制剂或受体）的特定位点起到调节剂的作用。借助程序DOTHELIX对该调节剂进行了计算机搜索。已表明具有与水蛭素相似区域的胸腺素I和P物质肽可抑制凝血酶活性。动力学数据表明这种抑制属于非竞争性抑制类型。关于凝血酶激活的蛋白C系统高反应性的数据证实了蛋白C是血液中产生凝血酶并与血栓调节蛋白相互作用时的首要防御机制这一观点。
