PDBsum entry 6jax

Hydrolase

PDB id: 6jax

Contents

Protein chain

377 a.a.

Ligands

NAG-NAG

GCS-GCS-GCS-GCS-GCS-GCS-GCS-GCS

Waters ×463

PDB id:

6jax

Name:

Hydrolase

Title:

Crystal structure of ostrinia furnacalis group ii chitinase catalytic domain 1 in complex with chitooctaose [(glcn)8]

Structure:

Group ii chitinase. Chain: a. Engineered: yes

Source:

Ostrinia furnacalis. Asian corn borer. Organism_taxid: 93504. Expressed in: komagataella pastoris gs115. Expression_system_taxid: 644223

Resolution:

1.70Å R-factor: 0.153 R-free: 0.179

Authors:

W.Chen,Y.Zhou,Q.Yang

Key ref:

W.Chen et al. (2019). Structural dissection reveals a general mechanistic principle for group II chitinase (ChtII) inhibition. J Biol Chem, 294, 9358-9364. PubMed id: 31053640 DOI: 10.1074/jbc.RA119.007812

Date:

25-Jan-19 Release date: 15-May-19

Protein chain

A0A221ZS22  (A0A221ZS22_OSTFU) -  Group II chitinase from Ostrinia furnacalis

Seq: 2929 a.a.

Struc: 377 a.a.*

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.2.1.14 - chitinase.
• Reaction: Hydrolysis of the 1,4-beta-linkages of N-acetyl-D-glucosamine polymers of chitin.

DOI no: 10.1074/jbc.RA119.007812

J Biol Chem 294:9358-9364 (2019)

PubMed id: 31053640

Structural dissection reveals a general mechanistic principle for group II chitinase (ChtII) inhibition.

W.Chen, Y.Zhou, Q.Yang.

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 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 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)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.