 |
PDBsum entry 6jax
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Structural dissection reveals a general mechanistic principle for group ii chitinase (chtii) inhibition.
|
|
|
Authors
|
|
W.Chen,
Y.Zhou,
Q.Yang.
|
|
|
Ref.
|
|
J Biol Chem, 2019,
294,
9358-9364.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
