Mechanism of metamifop inhibition of the carboxyltransferase domain of acetyl-coenzyme A carboxylase in Echinochloa crus-galli.

Xiangdong Xia,Wenjie Tang,Hongju Ma,Shun He,Jing Kang,Jianhong Li

doi:10.1038/srep34066

Xiangdong Xia, Wenjie Tang + Show 4 more

Open Access

https://doi.org/10.1038/srep34066

Copy DOI

Journal: Scientific Reports	Publication Date: Sep 26, 2016
Citations: 30	License type: CC BY 4.0

Affiliation: Huazhong Agricultural University

Abstract

Acetyl-coenzyme A carboxylase (ACCase) plays crucial roles in fatty acid metabolism and is an attractive target for herbicide discovery. Metamifop is a novel ACCase-inhibiting herbicide that can be applied to control sensitive weeds in paddy fields. In this study, the effects of metamifop on the chloroplasts, ACCase activity and carboxyltransferase (CT) domain gene expression in Echinochloa crus-galli were investigated. The results showed that metamifop interacted with the CT domain of ACCase in E. crus-galli. The three-dimensional structure of the CT domain of E. crus-galli ACCase in complex with metamifop was examined by homology modelling, molecular docking and molecular dynamics (MD) simulations. Metamifop has a different mechanism of inhibiting the CT domain compared with other ACCase inhibitors as it interacted with a different region in the active site of the CT domain. The protonation of nitrogen in the oxazole ring of metamifop plays a crucial role in the interaction between metamifop and the CT domain. The binding mode of metamifop provides a foundation for elucidating the molecular mechanism of target resistance and cross-resistance among ACCase herbicides, and for designing and optimizing ACCase inhibitors.

Highlights

Echinochloa crus-galli grown under control conditions (a) and with different doses of metamifop treatments (b-d: 12.5, 45, and 90 g a.i. ha−1) are presented
Computational simulations of the Setaria italica CT domain in complex with ACCase inhibitors suggested that the orientation of the carboxyl group of the inhibitors bound to the binding pocket differed, but these ACCase inhibitors can form a hydrogen-bond with the Ser[698] residue[15]
This study provides a foundation for elucidating the molecular mechanism of target resistance and cross-resistance among ACCase herbicides, and for designing and optimizing ACCase inhibitors

Summary

Introduction

Echinochloa crus-galli grown under control conditions (a) and with different doses of metamifop treatments (b-d: 12.5, 45, and 90 g a.i. ha−1) are presented. Computational simulations of the Setaria italica CT domain in complex with ACCase inhibitors suggested that the orientation of the carboxyl group of the inhibitors bound to the binding pocket differed, but these ACCase inhibitors can form a hydrogen-bond with the Ser[698] residue[15]. These results indicated that there are many different molecular mechanisms for inhibiting the CT domain, but these compounds may commonly bind with the CT domain. The structure of the CT domain of E. crus-galli ACCase in complex with metamifop was examined by homology modelling and molecular dynamics (MD) simulations. Molecular insight into the interactions between metamifop and the CT domain may aid in understanding the significance of the protonation of compounds

Methods

Results

Conclusion