Molecular Mechanism of Enantioselective Inhibition of Acetolactate Synthase by Imazethapyr Enantiomers

• Published in: Journal of agricultural and food chemistry Vol. 58; no. 7; pp. 4202 - 4206
• Main Authors: Zhou, Qingyan, Zhang, Na, Zhang, Cheng, Huang, Lidong, Niu, Yaofang, Zhang, Yongsong, Liu, Weiping
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 14-04-2010
• Subjects: acetolactate synthase; Acetolactate Synthase - antagonists & inhibitors; Acetolactate Synthase - chemistry; Biological and medical sciences; Chemical Aspects of Biotechnology/Molecular Biology; chemical concentration; chemical interactions; Down-Regulation; enantiomers; enzyme activity; enzyme inhibition; Enzyme Inhibitors - chemistry; Food industries; Fundamental and applied biological sciences. Psychology; Herbicides - chemistry; imazethapyr; in vivo studies; leaves; mechanism of action; Molecular Conformation; molecular models; Nicotinic Acids - chemistry; Plant Proteins - antagonists & inhibitors; Plant Proteins - chemistry; Protein Binding; Stereoisomerism; Structure-Activity Relationship; Zea mays; Zea mays - chemistry; Zea mays - enzymology; enantioselectivity; Imidazolinones; molecular mechanism; chiral; molecular docking; acetolactate synthase (ALS); Enantioselectivity; Enantiomer; Chiral compound; Inhibition; Mechanism
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf9038953

Chiral compounds usually behave enantioselectively in phyto-biochemical processes. Imidazolinones are a class of chiral herbicides that are widely used. They inhibit branched-chain amino acid biosynthesis in plants by targeting acetolactate synthase (ALS). It has been reported that the imidazolinone enantiomers show different inhibiting activities to maize (Zea mays L.) seedlings and ALS. However, to date, the mechanism of enantioselective inhibition of imazethapyr (IM) on ALS activity has not been well studied. In this study, pure enantiomers of IM were used for characterizing their differences in activity to ALS. Computational molecular docking was performed to discover the molecular interaction between IM enantiomers and ALS at the first time. Results showed that the IM enantiomers enantioselectively suppressed the in vitro and in vivo ALS activity of maize leaves. R-(−)-IM was more active than S-(+)-IM. The in vivo ALS activity study showed only a 2-fold difference between R-(−)-IM and S-(+)-IM. Quite different from the in vivo study, the in vitro study showed that the difference in inhibition between the enantiomers fell sharply as concentration increased. At the lowest concentration of 40 μg L−1, R-(−)-IM appeared 25 times more active than S-(+)-IM, but only 7 times at 200 μg L−1. At the highest concentration of 25 mg L−1, in vitro ALS activity was almost completely inhibited by S-(+)-, R-(−)-IM and (±)-IM, there was only 1.1 times differences between S-(+)- and R-(−)-IM. Molecular modeling results provide the rational structural basis to understand the mechanism of enantioselective inhibition of IM on ALS activity.