...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of molecular graphics & modelling >Understanding the molecular basis of stability in Kunitz (STI) family of inhibitors in terms of a conserved core tryptophan residue: A theoretical investigation
【24h】

Understanding the molecular basis of stability in Kunitz (STI) family of inhibitors in terms of a conserved core tryptophan residue: A theoretical investigation

机译：理解Kunitz（STI）抑制剂系列抑制剂稳定性的分子基础，在保守的核心色氨酸残留项方面：一个理论调查

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Graphical abstract Display Omitted Highlights ? M.D simulation is done with Kunitz (STI) family of inhibitors. ? Effect of core Tryptophan (W91) residue on protein stability has been assessed. ? Cavity created by mutation of tryptophan residue effects the folding pathway of Kunitz (STI) family. Abstract β-trefoil is one of the superfolds among proteins. Important classes of proteins like Interleukins (ILs), FibroblastGrowth Factors (FGFs), Kunitz (STI) family of inhibitors etc. belong to this fold. Kunitz (STI) family of inhibitors of proteins possess a highly conserved and structurally important Trytophan 91 (W91) residue, which stitches the top layer of the barrel with the lid. In this article we have investigated the molecular insights of the involvement of this W91 residue in the stability and folding pathway of Kunitz (STI) family. Winged bean Chymotrypsin inhibitor (WCI), a member of Kunitz (STI) family was chosen as a model system for carrying out the work. Molecular dynamics (MD) simulations were run with a set of total six proteins, including wild type WCI (WT) & five mutants namely W91F, W91M, W91A, W91H and W91I. Among all of them the coordinates of four proteins were taken from their crystal structures deposited in the Protein Data Bank (PDB), where as the coordinates for the rest two was generated using in-silico modelling. Our results suggest that truly this W91 residue plays a determining role in stability and folding pathway of Kunitz (STI) family. The mutants are less stable and more susceptible to quicker unfolding at higher temperatures compared to the wild type WCI. These effects are most pronounced for the smallest mutants namely W91H and W91A, indicating more is the cavity created by mutation at W91 position more the proteins becomes unstable. ]]>
机译：<！[cdata [ 图形抽象 显示省略 亮点 ？ MD仿真完成了Kunitz（STI）抑制剂系列。 ？ 核心尝试的效果已经评估了蛋白质稳定性的ptophan（W91）残留物。 ？ 通过色氨酸残留的突变产生的“全部”> kunitz（sti）家族的折叠通路。 抽象 β-三叶是蛋白质中的超折叠之一。重要的蛋白质类蛋白质（ILS），成纤维细胞生长因子（FGF），Kunitz（STI）抑制剂等属于这一折叠。 Kunitz（STI）蛋白质抑制剂系列具有高度保守和结构上重要的运动烷91（W91）残留物，其用盖子缝合枪管的顶层。在本文中，我们研究了该W91残留在Kunitz（STI）家族的稳定性和折叠途径中的分子见解。翼豆胰凝乳蛋白素抑制剂（WCI），Kunitz（STI）家族的成员被选为用于执行工作的模型系统。分子动力学（MD）模拟用一组总六种蛋白质进行，包括野生型WCI（WT）＆amp;五个突变体，即W91F，W91M，W91A，W91H和W91I。其中，从蛋白质数据库（PDB）中的沉积在沉积在沉积在蛋白质数据库（PDB）中的晶体结构中，在其间使用硅基模型产生四种蛋白质的坐标。我们的研究结果表明，真正的这款W91残留物在Kunitz（STI）家族的稳定性和折叠途径中起着确定的作用。与野生型WCI相比，突变体在更快的温度下更快地展开突变体更稳定并且更容易受到更容易展开。对于最小的突变体，这些效果是W91H和W91A最重要的，表明更多是通过W91的突变产生的腔体，蛋白质变得不稳定。 ]]>

著录项

相似文献

  • 外文文献
  • 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