Interactions of Aryloxyphenoxypropionic Acids with Sensitive and ResistantAcetyl-Coenzyme A Carboxylase by Homology Modeling and Molecular Dynamic Simulations
Acetyl-coenzyme A carboxylase (ACCase) has been identified as one of the most important targets of herbicides. In the present study, we constructed homology models of the carboxyl-transferase (CT) domain of ACCase from sensitive and resistant foxtail and used these models as templates to study the molecular mechanism of herbicide resistance and stereochemistry-activity relationships of aryloxyphenoxypropionates (APPs), In the homology modeling structures, the dimer of the CT domain was formed by the side-to-side arrangement of the two monomers, in such a way that the N domain of one molecule is placed next to the C domain of the other. The dimeric association of sensitive foxtail CT was found to differ from that of resistant foxtail CT, and the spatial orientation of two key residues, Leu-695 and Ile-695, in these dimers also differed. The mutation of He to Leu may perturb the conformation of the dimeric interface, which may account for the molecular mechanism of herbicide resistance. Further docking analysis indicated that the binding model of high-active compounds is similar to that in the crystal structure of the enzyme-ligand complex. The different spatial orientations of ester groups of the isomers of APPs may explain the stereochemistry-activity relationship. Ser-698 formed a H-bonding interaction with all of the docked iigands, while Tyr-728 formed a π-π stacking interaction with some of the APPs. These findings may enhance our understanding of the molecular mechanism of herbicide resistance and stereochemistry-activity relationships, which may provide a new starting point for the identification of more potent inhibitors against both sensitive and resistant ACCase.
Xiao-Lei Zhu Li Zhang Qiong Chen Jian Wan Guang-Fu Yang
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry,Central China Normal University, Wuhan 430079, Peoples Republic of China
国际会议
杭州
英文
1072-1079
2007-04-01（万方平台首次上网日期，不代表论文的发表时间）