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论文类型：期刊论文

发表时间：2019-06-14

发表刊物：JOURNAL OF BIOLOGICAL CHEMISTRY

收录刊物：SCIE、PubMed、EI

卷号：294

期号：24

页面范围：9358-9364

关键字：glycoside hydrolase; inhibitor; inhibition mechanism; insect; protein crystallization; Asian corn borer (Ostrinia furnacalis); ecdysis; group II chitinase; inhibitor design; X-ray crystallography

摘要：Small-molecule inhibitors of insect chitinases have potential applications for controlling insect pests. Insect group II chitinase (ChtII) is the most important chitinase in insects and functions throughout all developmental stages. However, the possibility of inhibiting ChtII by small molecules has not been explored yet. Here, we report the structural characteristics of four molecules that exhibited similar levels of inhibitory activity against OfChtII, a group II chitinase from the agricultural pest Asian corn borer Ostrinia furnacalis. These inhibitors were chitooctaose ((GlcN)(8)), dipyrido-pyrimidine derivative (DP), piperidine-thienopyridine derivative (PT), and naphthalimide derivative (NI). The crystal structures of the OfChtII catalytic domain complexed with each of the four inhibitors at 1.4-2.0 resolutions suggested they all exhibit similar binding modes within the substrate-binding cleft; specifically, two hydrophobic groups of the inhibitor interact with +1/+2 tryptophan and a -1 hydrophobic pocket. The structure of the (GlcN)(8) complex surprisingly revealed that the oligosaccharide chain of the inhibitor is orientated in the opposite direction to that previously observed in complexes with other chitinases. Injection of the inhibitors into 4th instar O. furnacalis larvae led to defects in development and pupation. The results of this study provide insights into a general mechanistic principle that confers inhibitory activity against ChtII, which could facilitate rational design of agrochemicals that target ecdysis of insect pests.