title: Molecular mechanism of enantioselective inhibition of acetolactate synthase by imazethapyr enantiomers.
abstract: 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 microg L(-1), R-(-)-IM appeared 25 times more active than S-(+)-IM, but only 7 times at 200 microg 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.
authors.affiliation: Ministry of Education Key Laboratory of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Zhou
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Lidong
authors.initials: L
authors.lastname: Huang
authors.forename: Yaofang
authors.initials: Y
authors.lastname: Niu
authors.forename: Yongsong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Weiping
authors.initials: W
authors.lastname: Liu
mesh_terms: D000095:Acetolactate Synthase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006540:Herbicides / Q000737:chemistry; D008968:Molecular Conformation; D009539:Nicotinic Acids / Q000737:chemistry*; D010940:Plant Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011485:Protein Binding; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D003313:Zea mays / Q000737:chemistry / Q000201:enzymology*
chemical_list: D004791:Enzyme Inhibitors; D006540:Herbicides; D009539:Nicotinic Acids; D010940:Plant Proteins; C093630:imazethapyr; D000095:Acetolactate Synthase