High throughput receptor-based virtual screening under ZINC database, synthesis, and biological evaluation of ketol-acid reductoisomerase inhibitors.
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.
Liu
Xing-Hai
XH
Nankai University, Tianjin, China.
Chen
Pei-Quan
PQ
Wang
Bao-Lei
BL
Dong
Wei-Li
WL
Li
Yong-Hong
YH
Xie
Xing-Qiao
XQ
Li
Zheng-Ming
ZM
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
D004791:Enzyme Inhibitors; D050540:Ketol-Acid Reductoisomerase