...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >A Distal Loop Controls Product Release and Chemo- and Regioselectivity in Cytochrome P450 Decarboxylases
【24h】

A Distal Loop Controls Product Release and Chemo- and Regioselectivity in Cytochrome P450 Decarboxylases

机译：远端环路控制细胞色素P450脱羧酶中的产品释放和化学和地区选择性

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

Cytochrome P450 OleT utilizes hydrogen peroxide (H_(2)O_(2)) to catalyze the decarboxylation or hydroxylation of fatty acid (FA) substrates. Both reactions are initiated through the abstraction of a substrate hydrogen atom by the high-valent iron–oxo intermediate known as Compound I. Here, we specifically probe the influence of substrate coordination on OleT reaction partitioning through the combined use of fluorescent and electron paramagnetic resonance (EPR)-active FA probes and mutagenesis of a structurally disordered F–G loop that is distal from the heme-iron active site. Both probes are efficiently metabolized by OleT and efficiently trigger the formation of Compound I. Transient fluorescence and EPR reveal a slow product release step, mediated by the F–G loop, that limits OleT turnover. A single-amino acid change or excision of the loop reveals that this region establishes critical interactions to anchor FA substrates in place. The stabilization afforded by the F–G loop is essential for regulating regiospecific C–H abstraction and allowing for efficient decarboxylation to occur. These results highlight a regulatory strategy whereby the fate of activated oxygen species can be controlled at distances far removed from the site of chemistry.
机译：细胞色素P450 OLET利用过氧化氢（H_（2）O_（2））催化脂肪酸（FA）底物的脱羧或羟基化。通过称为化合物I的高价铁铁 - 氧代中间体的底物氢原子的抽象引发了两种反应。在这里，我们特别探讨了通过组合使用荧光和电子顺磁共振的OLET反应分配对OLET反应划分的影响（EPR） - 与血红素铁活性位点远端的结构紊乱的F-G环的 - 活性FA探针和诱变。通过OLet有效地代谢并有效地触发化合物I的形成。瞬时荧光和EPR揭示由F-G环介导的缓慢产物释放步骤，限制OLET周转。环路的单氨基酸变化或切除揭示了该区域与锚固FA基板建立关键相互作用。由F-G环提供的稳定化对于调节细胞特异性C-H抽象并允许有效的脱羧剂发生。这些结果突出了调节策略，即可在远离化学位点移除的距离处控制活性氧物质的命运。

著录项

  • 来源
    《Biochemistry》 |2018年第3期|共10页
  • 作者

    José A. Amaya; Cooper D. Rutland; Nicholas Leschinsky; Thomas M. Makris;

  • 作者单位

    Department of Chemistry and Biochemistry University of South Carolina Columbia South Carolina 29208 United States;

    Department of Chemistry and Biochemistry University of South Carolina Columbia South Carolina 29208 United States;

    Department of Chemistry and Biochemistry University of South Carolina Columbia South Carolina 29208 United States;

    Department of Chemistry and Biochemistry University of South Carolina Columbia South Carolina 29208 United States;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
  • 关键词

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