6JAV

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

Summary for 6JAV

• Entry DOI: 10.2210/pdb6jav/pdb
• Descriptor: Group II chitinase, 2-{[(4-chlorophenyl)methyl]sulfanyl}-7-methyl-N-(prop-2-en-1-yl)-7,8-dihydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-amine, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: inhibitor complex, chitinase, hydrolase
• Biological source: Ostrinia furnacalis (Asian corn borer)
• Total number of polymer chains: 1
• Total formula weight: 45104.58

Authors

Chen, W.,Zhou, Y.,Yang, Q. (deposition date: 2019-01-25, release date: 2019-05-15, Last modification date: 2023-11-22)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.437 Å)