Analysis of a Critical Residue Determining Herbicide Efficiency Sensitivity in Carboxyltransferase Domain of Acetyl-CoA Carboxylase from Poaceae by Homology Modeling and Free Energy Simulation

作     者：TAO Jin ZHAO Bo TIAN Xue-mei ZHENG Liang-yu CAO Shu-gui 

作者机构：Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education Jilin University Changchun 130021 P. R. China 

出 版 物：《Chemical Research in Chinese Universities》 (高等学校化学研究（英文版）)

年 卷 期：2010年第26卷第5期

页      面：816-821页

核心收录：

学科分类：090403[农学-农药学(可授农学、理学学位）] 09[农学] 0904[农学-植物保护] 

基　　金：Supported by the National Natural Science Foundation of China(Nos.20802025  30870539  20432010 and 20672045) 

主　　题：Molecular modeling Molecular dynamics Free energy calculation Herbicide resistance 

摘      要：Carboxyltransferase domain（CT） of acetyl-coenzyme A carboxylase（ACCase, EC 6.***.1.2） from a family of Poaceae is an important target of commercial herbicide APPs for controlling grass weed growth. As the abuse of APPs herbicides, the resistant ACCase due to the mutation of a single residue（Ile→Leu）, which is located in CT active site, is emergent in many populations and species of Poaceae. So it is urgent to understand the resistant mechanism so as to design new effect herbicides. Herein lies the complex of CT dimmer from Lolium rigidum and herbicide haloxyfop successfully constructed for wild type enzyme and Ile/Leu mutant, respectively, providing a basis for explaining the resistance from microscopic structure. Moreover, the binding free energy difference between wild type and mutant enzymes was predicted in good agreement with the known observation, and the various contributions to it were analyzed, by Molecular mechanics-Poisson-Boltzmann surface area（MM-PBSA） method. The results indicate the van der Waals interaction difference between the protein and inhibitor, -22.94 kJ/mol of CT wild type lower than that of mutant, is the major reason for resistance. Structure analysis further suggests that van der Waals interaction difference is originated from the steric hindrance between the side chain of mutated residue Leu and the chiral methyl group of haloxyfop. All these findings enhance the understanding of resistant mechanism of ACCase to herbicide by Ile/Leu mutation and provide an important clue for the rational design of high effective herbicides.