Identification of some novel AHAS inhibitors via molecular docking and virtual screening approach.
Acetohydroxyacid synthase (AHAS; EC 2.2.1.6) catalyzes the first common step in branched-chain amino acid biosynthesis. This enzyme is an important target for the design of environmental-benign herbicides. Based on the crystal structure of AHAS/sulfonylurea complex, we have carried out computational screening of the ACD-3D database in order to look for novel non-sulfonylurea inhibitors of AHAS for the first time. Three novel compounds were found to inhibit plant AHAS in vitro among 14 procured compounds. One compound showed promising activity in vivo for rape root growth inhibition bioassay. This research provided useful clues for further design and discovery of AHAS inhibitors.
Wang
Jian-Guo
JG
State-Key Laboratory of Elemento-Organic Chemistry, National Pesticide Engineering Research Center, Nankai University, Tianjin 300071, China.
Xiao
Yong-Jun
YJ
Li
Yong-Hong
YH
Ma
Yi
Y
Li
Zheng-Ming
ZM
D000095:Acetolactate Synthase / Q000037:antagonists & inhibitors*; D017360:Arabidopsis / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D001665:Binding Sites; D001681:Biological Assay; D029741:Brassica rapa / Q000187:drug effects / Q000254:growth & development; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D016208:Databases, Factual; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006540:Herbicides / Q000737:chemistry* / Q000494:pharmacology; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D008970:Molecular Weight; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D006540:Herbicides; D008024:Ligands; D000095:Acetolactate Synthase