...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The journal of physical chemistry, A. Molecules, spectroscopy, kinetics, environment, & general theory >The α-amino group of the threonine substrate as the general base during tRNA aminoacylation: A new version of substrate-assisted catalysis predicted by hybrid DFT
【24h】

The α-amino group of the threonine substrate as the general base during tRNA aminoacylation: A new version of substrate-assisted catalysis predicted by hybrid DFT

机译：苏氨酸底物的α-氨基作为tRNA氨酰化过程中的一般碱基：杂化DFT预测的底物辅助催化的新形式

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

Density functional theory-based methods in combination with large chemical models have been used to investigate the mechanism of the second half-reaction catalyzed by Thr-tRNA synthetase: aminoacyl transfer from Thr-AMP onto the A76~3′OH of the cognate tRNA. In particular, we have examined pathways in which an active site His309 residue is either protonated or neutral (i.e., potentially able to act as a base). In the protonated His309-assisted mechanism, the rate-limiting step is formation of the tetrahedral intermediate. The barrier for this step is 155.0 kJ mol~(-1), and thus, such a pathway is concluded to not be enzymatically feasible. For the neutral His309-assisted mechanism, two models were used with the difference being whether Lys465 was included. For either model, the barrier of the rate-limiting step is below the upper thermodynamic enzymatic limit of ～125 kJ mol~(-1). Specifically, without Lys465, the rate-limiting barrier is 122.1 kJ mol ~(-1) and corresponds to a rotation about the tetrahedral intermediate C_(carb)-OH bond. For the model with Lys465, the rate-limiting barrier is slightly lower and corresponds to the formation of the tetrahedral intermediate. Importantly, for both "neutral His309" models, the neutral amino group of the threonyl substrate directly acts as the proton acceptor; in the formation of the tetrahedral intermediate, the _(A76)3′OH proton is directly transferred onto the Thr-NH _2. Therefore, the overall mechanism follows a general substrate-assisted catalytic mechanism.
机译：基于密度泛函理论的方法与大型化学模型已被用于研究由Thr-tRNA合成酶催化的第二个半反应的机理：氨酰从Thr-AMP转移到同源tRNA的A76〜3'OH上。特别地，我们已经研究了其中活性位点His309残基是质子化或中性的（即潜在地可以充当碱基）的途径。在质子化的His309辅助机制中，限速步骤是形成四面体中间体。该步骤的障碍是155.0 kJ mol〜（-1），因此，该途径被认为在酶学上是不可行的。对于中性His309辅助机制，使用了两种模型，不同之处在于是否包括Lys465。对于任何一种模型，限速步骤的障碍都在〜125 kJ mol〜（-1）的热力学酶解上限以下。具体地，在没有Lys465的情况下，限速势垒为122.1kJ mol〜（-1），并且对应于围绕四面体中间C_（carb）-OH键的旋转。对于具有Lys465的模型，限速屏障稍低，并且对应于四面体中间体的形成。重要的是，对于两个“中性His309”模型，苏氨酰底物的中性氨基都直接充当质子受体。在四面体中间体的形成中，_（A76）3'OH质子直接转移到Thr-NH _2上。因此，总体机理遵循一般的底物辅助催化机理。

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