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首页> 外文期刊>Biochemistry >An ester bond linking a fragment of a serine proteinase to its serpin inhibitor
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An ester bond linking a fragment of a serine proteinase to its serpin inhibitor

机译：连接丝氨酸蛋白酶片段与其丝氨酸蛋白酶抑制剂的酯键

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Most known members of the serpin superfamily are serine proteinase inhibitors. Serpins are therefore important regulators of blood coagulation, complement activation, fibrinolysis, and turnover of extracellular matrix. Serpins form SDS-resistant complexes of 1:1 stoichiometry with their target proteinases by reaction of their P-1-P-1' peptide bond with the active site of the proteinases. The nature of the interactions responsible for the high stability of the complexes is a controversial issue. We subjected the complex between the serine proteinase urokinase-type plasminogen activator (uPA) and the serpin plasminogen activator inhibitor-1 (PAI-1) to proteolytic digestion under nondenaturing conditions. The complex could be degraded to a fragment containing two disulfide-linked peptides from uPA, one of which included the active site Ser, while PAI-1 was left undegraded. By further proteolytic digestion after denaturation and reduction, it was also possible to degrade the PAI-1 moiety, and we isolated a fragment containing 10 amino acids from uPA, encompassing the active site Ser, and 6 amino acids from PAI-1, including the P-1 Arg. Characterization of the fragment gave results fully in agreement with the hypothesis that it contained an ester bond between the hydroxyl group of the active site Ser and the carboxyl group of the P-1 Arg. These data for the first time provide direct evidence that serine proteinases are entrapped at an acyl intermediate stage in serine proteinase-serpin complexes. [References: 24]
机译：丝氨酸蛋白酶抑制剂超家族的最已知成员是丝氨酸蛋白酶抑制剂。因此丝氨酸蛋白酶抑制剂是血液凝固，补体激活，纤维蛋白溶解和细胞外基质更新的重要调节剂。丝氨酸蛋白酶抑制剂通过其P-1-P-1'肽键与蛋白酶的活性位点反应，与目标蛋白酶形成抗SDS化学计量比为1：1的复合物。引起配合物高稳定性的相互作用的性质是一个有争议的问题。我们使丝氨酸蛋白酶尿激酶型纤溶酶原激活物（uPA）和丝氨酸蛋白酶抑制剂纤溶酶原激活物抑制剂-1（PAI-1）之间的复合物在非变性条件下进行蛋白水解消化。可以将复合物降解为包含来自uPA的两个二硫键连接肽的片段，其中一个包含活性位点Ser，而PAI-1未被降解。通过变性和还原后进一步的蛋白水解消化，还可以降解PAI-1部分，我们从uPA中分离了一个包含10个氨基酸的片段，包括活性位点Ser，从PAI-1中分离了6个氨基酸，其中包括P-1精氨酸。对该片段的表征给出了与以下假设完全一致的假说：该假说在活性位点Ser的羟基和P-1 Arg的羧基之间包含一个酯键。这些数据首次提供了直接证据，表明丝氨酸蛋白酶在丝氨酸蛋白酶-丝氨酸蛋白酶抑制剂复合物中的酰基中间阶段被捕获。 [参考：24]

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