...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Electrostatic Fields near the Active Site of Human Aldose Reductase: 2. New Inhibitors and Complications Caused by Hydrogen Bonds
【24h】

Electrostatic Fields near the Active Site of Human Aldose Reductase: 2. New Inhibitors and Complications Caused by Hydrogen Bonds

机译：人类醛糖还原酶活性位点附近的静电场：2.氢键引起的新抑制剂和并发症

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

Vibrational Stark effect spectroscopy was used to measure electrostatic fields in the hydrophobic region of the active site of human aldose reductase (hALR2). A new nitrile-containing inhibitor was designed and synthesized, and the X-ray structure of its complex, along with cofactor NADP~+, with wild-type hALR2 was determined at 1.3 A resolution. The nitrile is found to be in the proximity of T113, consistent with a hydrogen bond interaction. Two vibrational absorption peaks were observed at room temperature in the nitrile region when the inhibitor binds to wild-type hALR2, indicating that the nitrile probe experiences two different microenvironments, and these could be empirically separated into a hydrogen-bonded and non-hydrogen-bonded population by comparison with the T113A mutant, in which a hydrogen bond to the nitrile is not present. Classical molecular dynamics simulations based on the structure predict a double-peak distribution in protein electric fields projected along the nitrile probe. The interpretation of these two peaks as a hydrogen bond formation-dissociation process between the probe nitrile group and a nearby amino acid side chain is used to explain the observation of two IR bands, and the simulations were used to investigate the molecular details of this conformational change. Hydrogen bonding complicates the simplest analysis of vibrational frequency shifts as being due solely to electrostatic interactions through the vibrational Stark effect, and the consequences of this complication are discussed.
机译：使用振动斯塔克效应光谱法测量人醛糖还原酶（hALR2）活性位点的疏水区域中的静电场。设计并合成了一种新的含腈抑制剂，并以1.3 A的分辨率测定了其配合物与辅因子NADP〜+与野生型hALR2的X射线结构。发现腈位于T113的附近，与氢键相互作用一致。当抑制剂与野生型hALR2结合时，在室温下在腈区域观察到两个振动吸收峰，表明腈探针经历了两个不同的微环境，根据经验它们可以分为氢键和非氢键。与T113A突变体（其中不存在与腈的氢键）相比，该群体的数量增加。基于该结构的经典分子动力学模拟可预测沿腈探针投射的蛋白质电场中的双峰分布。解释这两个峰为探针腈基和附近氨基酸侧链之间的氢键形成-解离过程，以解释两个IR谱带的观察结果，并通过模拟研究该构象的分子细节。更改。氢键键合使振动频移的最简单分析变得复杂，这仅归因于通过振动斯塔克效应产生的静电相互作用，并讨论了这种并发症的后果。

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