...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Molecular dynamics studies of ground state and intermediate of the hyperthermophilic indole-3-glycerol phosphate synthase
【24h】

Molecular dynamics studies of ground state and intermediate of the hyperthermophilic indole-3-glycerol phosphate synthase

机译：嗜热吲哚-3-甘油磷酸合酶基态和中间体的分子动力学研究

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

Indole-3-glycerol phosphate synthase catalyzes the terminal ring closure step in tryptophan biosynthesis. In this paper, we compare the results from molecular dynamics (MD) simulations of enzyme-bound substrate at 298, 333, 363, and 385 K and the enzyme-bound intermediate at 385 K, solvated in TIP3P water box with a CHARMM force field. Results from MD simulations agree with experimental studies supporting the observation that Lys-110 is the general acid. Based on its location in the active site during the MD simulations, Glu-2110 warrants classification as the general base instead of the previously proposed Glu-159. We find that the relative population of the reactive enzyme-substrate Michaelis conformers [near attack conformers (NACs)] with temperature correlates well (correlation coefficient of 0.96) with the relative activity of this thermophilic enzyme. At higher temperature, the enzyme-substrate electrostatic interaction favors the binding of the substrate in NAC conformation, whereas, at lower temperature, the substrate is distorted and bound in a nonreactive conformation. This change is reflected in the approximate to1,100-fold increase in population of NACs at 385 K relative to 298 K. The easily determined population of NACs at given temperature tells much about the thermophilic property of the enzyme. Thus, the hyperthermophilic enzyme has evolved to have optimum activity at high temperatures, and, with lowering of the temperature, the electrostatic interaction at the. active site is enhanced and the structure is deformed. This model can be regarded as a general explanation for the activity of hyperthermophilic enzymes.
机译：吲哚-3-甘油磷酸合酶催化色氨酸生物合成中的末端闭环步骤。在本文中，我们比较了在CHARMM力场中溶解在TIP3P水箱中的298、333、363和385 K处酶结合的底物与385 K处酶结合的中间体的分子动力学（MD）模拟结果。 MD模拟的结果与实验研究一致，支持了Lys-110是一般酸的观察。根据其在MD模拟过程中在活动站点中的位置，Glu-2110可以作为一般基础而不是先前提出的Glu-159进行分类。我们发现反应性酶-底物Michaelis构象异构体[近攻击构象异构体（NAC）]与温度的相对相关性与该嗜热酶的相对活性相关性很好（相关系数为0.96）。在较高温度下，酶-底物静电相互作用有利于底物以NAC构象结合，而在较低温度下，底物变形并以非反应构象结合。这种变化反映在385 K时相对于298 K的NAC群体大约增加了1100倍。在给定温度下易于确定的NAC群体充分说明了该酶的嗜热特性。因此，高温嗜热酶已经进化为在高温下具有最佳活性，并且随着温度的降低，高温下的静电相互作用。活动部位增强，结构变形。该模型可以被视为对超嗜热酶活性的一般解释。

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