Molecular Mechanism of λ-Cyhalothrin Detoxification by a Delta-Class Glutathione S-Transferase (PxGSTD3) from <i>Plutella xylostella</i>

The diamondback moth (<i>Plutella xylostella</i>) exhibits significant resistance to commonly used insecticides including λ-cyhalothrin. Delta-class glutathione S-transferases (GSTs) are crucial detoxification enzymes involved in insecticide detoxification and resistance. We demonstrate that <i>PxGSTD3</i> is associated with the resistance to λ-cyhalothrin and contributes to λ-cyhalothrin detoxification. The transcription of <i>PxGSTD3</i> was rapidly upregulated in response to λ-cyhalothrin exposure, and the recombinant protein exhibited significant metabolic activity against λ-cyhalothrin. Further investigation using computer-aided drug design revealed the binding and metabolic mechanism of PxGSTD3 toward λ-cyhalothrin. The results showed that λ-cyhalothrin binds to an active pocket through noncovalent interactions such as hydrogen bonds, π-π stacking, and hydrophobic interactions. Residues Arg36, Tyr115, and Phe119 were found to have a critical impact on the binding and metabolism of λ-cyhalothrin by PxGSTD3. These findings provide valuable insights into the metabolic role of GST in detoxifying insecticides and offer theoretical guidance for the design of novel pyrethroid-based insecticides.