6JAY

Crystal structure of Ostrinia furnacalis Group II chitinase catalytic domain 1 in complex with a dipyrido-pyrimidine derivative

6JAY の概要

• エントリーDOI: 10.2210/pdb6jay/pdb
• 関連するPDBエントリー: 5Y29
• 分子名称: Group II chitinase, 2-acetamido-2-deoxy-beta-D-glucopyranose, 2-amino-1-[(furan-2-yl)methyl]-5-oxo-3-({[(2S)-oxolan-2-yl]methyl}carbamoyl)-5H-dipyrido[1,2-a:2',3'-d]pyrimidin-1-ium, ... (4 entities in total)
• 機能のキーワード: inhibitor complex, chitinase, hydrolase
• 由来する生物種: Ostrinia furnacalis (Asian corn borer)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45110.04

構造登録者

Chen, W.,Zhou, Y.,Yang, Q. (登録日: 2019-01-25, 公開日: 2019-05-15, 最終更新日: 2024-11-13)

主引用文献

Chen, W.,Zhou, Y.,Yang, Q.
Structural dissection reveals a general mechanistic principle for group II chitinase (ChtII) inhibition.
J.Biol.Chem., 294:9358-9364, 2019

PubMed Abstract: 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 ChtII, a group II chitinase from the agricultural pest Asian corn borer These inhibitors were chitooctaose ((GlcN)), dipyrido-pyrimidine derivative (DP), piperidine-thienopyridine derivative (PT), and naphthalimide derivative (NI). The crystal structures of the ChtII catalytic domain complexed with each of the four inhibitors at 1.4-2.0 Å 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) 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 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.

PubMed: 31053640
DOI: 10.1074/jbc.RA119.007812

実験手法

X-RAY DIFFRACTION (1.498 Å)