Understanding Resistance Mechanism of Protoporphyrinogen Oxidase-Inhibiting Herbicides: Insights from Computational Mutation Scanning and Site-Directed Mutagenesis
Understanding Resistance Mechanism of Protoporphyrinogen Oxidase-Inhibiting Herbicides: Insights from Computational Mutation Scanning and Site-Directed Mutagenesis
复制标题
了解原卟啉原氧化酶抑制性除草剂的抗性机制：来自计算突变扫描和定点诱变的见解
DOI：
10.1021/jf5018115
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发表时间：
2014-07-23
影响因子：
6.1
通讯作者：
Yang, Guang-Fu
中科院分区：
文献类型：
--
作者：
Hao, Ge-Fei;Tan, Ying;Yang, Guang-Fu
利用计算突变扫描（CMS）技术研究了原卟啉原氧化酶（PPO）对5种PPO抑制剂除草剂的抗性潜力，为PPO抑制剂的抗性机制和结构-抗性关系提供了有价值的见解。突变引起的结合自由能的计算值与PPO定点突变获得的相应实验数据非常相关，从而为PPO抑制剂的抗性机制提供了有价值的见解。计算的熵变与抑制剂的构象柔性有关，这表明具有适当构象柔性的抑制剂可以同时抑制野生型和突变体。计算数据与实验数据之间的合理相关性进一步验证了CMS方案对于预测与靶蛋白上的氨基酸突变相关的抗性是有价值的。
The potential of protoporphyrinogen oxidase (PPO) to develop resistance against five PPO-inhibiting herbicides has been studied using computational mutation scanning (CMS) protocol, leading to valuable insights into the resistance mechanisms and structure-resistance relationship of the PPO inhibitors. The calculated shifts in the binding free energies caused by the mutations correlated very well with those derived from the corresponding experimental data obtained from site-directed mutagenesis of PPO, leading to valuable insights into the resistance mechanisms of PPO inhibitors. The calculated entropy change was related to the conformational flexibility of the inhibitor, which demonstrated that inhibitors with appropriate conformational flexibility may inhibit both the wild type and mutants simultaneously. The reasonable correlation between the computational and experimental data further validate that CMS protocol is valuable for predicting resistance associated with amino acid mutations on target proteins.