...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Interconversion of active and inactive conformations of urokinase-type plasminogen activator
【24h】

Interconversion of active and inactive conformations of urokinase-type plasminogen activator

机译：尿激酶型纤溶酶原激活剂的活性和非活性构象的相互转化

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The catalytic activity of serine proteases depends on a salt-bridge between the amino group of residue 16 and the side chain of Asp194. The salt-bridge stabilizes the oxyanion hole and the S1 specificity pocket of the protease. Some serine proteases exist in only partially active forms, in which the amino group of residue 16 is exposed to the solvent. Such a partially active state is assumed by a truncated form of the murine urokinase-type plasminogen activator (muPA), consisting of residues 16-243. Here we investigated the allosteric interconversion between partially active states and the fully active state. Both a monoclonal antibody (mU3) and a peptidic inhibitor (mupain-1-16) stabilize the active state. The epitope of mU3 is located in the 37- and 70-loops at a site homologous to exosite I of thrombin. The N-terminus~((Ile16)) of muPA~((16-243)) was less exposed upon binding of mU3 or mupain-1-16. In contrast, introduction of the mutations F40Y or E137A into muPA~((16-243)) increased exposure of the N-terminus~((Ile16)) and resulted in large changes in the thermodynamic parameters for mupain-1-16 binding. We conclude that the distorted state of muPA~((16-243)) is conformationally ordered upon binding of ligands to the active site and upon binding of mU3 to the 37- and 70-loops. Our study establishes the 37- and 70-loops as a unique site for binding to compounds stabilizing the active state of serine proteases.
机译：丝氨酸蛋白酶的催化活性取决于残基16的氨基和Asp194的侧链之间的盐桥。盐桥稳定了蛋白酶的氧阴离子孔和S1特异性口袋。一些丝氨酸蛋白酶仅以部分活性形式存在，其中残基16的氨基暴露于溶剂。鼠尿激酶型纤溶酶原激活物（muPA）的截短形式由残基16-243构成，具有这种部分活性状态。在这里，我们研究了部分活动状态和完全活动状态之间的变构相互转换。单克隆抗体（mU3）和肽类抑制剂（mupain-1-16）均可稳定活性状态。 mU3的表位位于与凝血酶的异位点I同源的位点的37环和70环中。当结合mU3或mupain-1-16时，muPA-（（16-243））的N-末端（（Ile16））暴露较少。相反，将突变F40Y或E137A引入muPA〜（（16-243））会增加N端〜（（Ile16））的暴露，并导致mupain-1-16结合的热力学参数发生较大变化。我们得出结论，在配体与活性位点结合以及在mU3与37和70环结合后，muPA〜（（16-243））的扭曲状态在构象上是有序的。我们的研究建立了37和70环作为与稳定丝氨酸蛋白酶活性状态的化合物结合的独特位点。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号