title: High throughput receptor-based virtual screening under ZINC database, synthesis, and biological evaluation of ketol-acid reductoisomerase inhibitors.
abstract: Ketol-acid reductoisomerase (KARI; EC 1.1.1.86) catalyzes the second common step in branched-chain amino acid biosynthesis. This enzyme is an important target for drug design. Based on the crystal structure of ketol-acid reductoisomerase/N-hydroxy-N-isopropyloxamate (IpOHA) complex, we have carried out high throughput receptor-based virtual screening of the ZINC/drug like database (2 000 000 compounds) to look for novel inhibitors of KARI for the first time. Some novel compounds were found to inhibit rice KARI in vitro among 15 procured compounds. This method can provide useful information for further design and discovery of KARI inhibitors.
authors.affiliation: Nankai University, Tianjin, China.
authors.forename: Xing-Hai
authors.initials: XH
authors.lastname: Liu
authors.forename: Pei-Quan
authors.initials: PQ
authors.lastname: Chen
authors.forename: Bao-Lei
authors.initials: BL
authors.lastname: Wang
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Dong
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Li
authors.forename: Xing-Qiao
authors.initials: XQ
authors.lastname: Xie
authors.forename: Zheng-Ming
authors.initials: ZM
authors.lastname: Li
mesh_terms: D020134:Catalytic Domain; D016208:Databases, Factual; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D057166:High-Throughput Screening Assays; D050540:Ketol-Acid Reductoisomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding
chemical_list: D004791:Enzyme Inhibitors; D050540:Ketol-Acid Reductoisomerase