• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Chemistry: A European journal >Investigation of the Hydroxylation Mechanism of Noncoupled Copper Oxygenases by Ab Initio Molecular Dynamics Simulations
【24h】

Investigation of the Hydroxylation Mechanism of Noncoupled Copper Oxygenases by Ab Initio Molecular Dynamics Simulations

机译：从头算分子动力学模拟研究非偶联铜氧合酶的羟化机理

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

In Nature, the family of copper monooxygenases comprised of peptidylglycine a-hydroxylating monooxygenase (PHM), dopamine β-monooxygenase (DβM), and tyramine β-monooxygenase (TβM) is known to perform dioxygen-dependent hydroxylation of aliphatic C-H bonds by using two uncoupled metal sites. In spite of many investigations, including biochemical, chemical, and computational, details of the C-H bond oxygenation mechanism remain elusive. Herein we report an investigation of the mechanism of hydroxylation by PHM by using hybrid quantum/classical potentials (i.e., QM/MM). Although previous investigations using hybrid QM/ MM techniques were restricted to geometry optimizations, we have carried out ab initio molecular dynamics simulations in order to include the intrinsic flexibility of the active sites in the modeling protocol. The major finding of this study is an extremely fast rebound step after the initial hydrogenabstraction step promoted by the cupric–superoxide adduct. The hydrogen- abstraction/rebound sequence leads to the formation of an alkyl hydroperoxide intermediate. Long-range electron transfer from the remote copper site subsequently triggers its reduction to the hydroxylated substrate. We finally show two reactivity consequences inherent in the new mechanistic proposal, the investigation of which would provide a means to check its validity by experimental means.
机译：在自然界中，已知由肽基甘氨酸α-羟基化单加氧酶（PHM），多巴胺β-单加氧酶（DβM）和酪胺β-单加氧酶（TβM）组成的铜单加氧酶家族可通过使用两种来进行脂肪族CH键的双氧依赖性羟基化非耦合金属站点。尽管进行了包括生化，化学和计算在内的许多研究，但C-H键氧合机理的细节仍然难以捉摸。本文中，我们报告了通过使用混合量子/经典电势（即QM / MM）对PHM进行羟基化的机理的研究。尽管以前使用混合QM / MM技术进行的研究仅限于几何优化，但是我们已经进行了从头算分子动力学模拟，以便在建模协议中包括活动位点的固有灵活性。这项研究的主要发现是铜-超氧化物加合物促进了最初的吸氢步骤之后的极快的回弹步骤。氢提取/回弹序列导致烷基氢过氧化物中间体的形成。从远程铜位置进行的远程电子转移随后触发了其还原到羟基化底物的过程。我们最终展示了新机制提案中固有的两个反应性后果，对其进行研究将提供一种通过实验手段检查其有效性的手段。

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