Modulation of protein-protein interactions by synthetic receptors: Design of molecules that disrupt serine protease-proteinaceous inhibitor interaction
Modulation of protein-protein interactions by synthetic receptors: Design of molecules that disrupt serine protease-proteinaceous inhibitor interaction
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DOI：
10.1073/pnas.082675899
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发表时间：
2002-04-16
影响因子：
11.1
通讯作者：
Hamilton, AD
中科院分区：
文献类型：
--
作者：
Park, HS;Lin, Q;Hamilton, AD
在本文中，我们描述了一种合成受体的设计和评估，该受体与胰凝乳蛋白酶的外表面结合，并破坏其与蛋白质抑制剂的相互作用，例如大豆胰蛋白酶抑制剂、碱性胰腺胰蛋白酶抑制剂、火鸡卵粘蛋白抑制剂和鲍曼-伯克抑制剂。使用酶动力学、非变性凝胶电泳和凝胶过滤层析，我们表明该受体在阻断胰凝乳蛋白酶-大豆胰蛋白酶抑制剂复合物方面特别有效，并且其机制涉及初始三元复合物的形成，然后是蛋白质抑制剂的时间依赖性置换。
In the present article we describe the design and evaluation of a synthetic receptor that binds to the exterior surface of chymotrypsin and disrupts its interaction with proteinaceous inhibitors, such as soybean trypsin inhibitor, basic pancreatic trypsin inhibitor, ovomucoid turkey inhibitor, and Bowman-Birk inhibitor. Using enzyme kinetics, nondenaturing gel electrophoresis, and gel filtration chromatography we show that the receptor is particularly effective at blocking the chymotrypsin-soybean trypsin inhibitor complex and that the mechanism involves formation of an initial ternary complex followed by a time-dependent displacement of the proteinaceous inhibitor.