Resistance Mechanism of Plutella xylostella (L.) Associated with Amino Acid Substitutions in Acetylcholinesterase-1: Insights from Homology Modeling, Docking and Molecular Dynamic Simulation.

Simple Summary: One of the most destructive pests of cruciferous plants that quickly develops resistance to most pesticide groups is Plutella xylostella. Investigating the resistant strain of P. xylostella revealed the molecular mechanisms underlying resistance to chlorpyrifos, concentrating specifically on the ace1 gene. The sequencing results revealed amino acid substitutions in ace1 of the resistant strain. The structures of the wild-type and mutant ace1 strains were compared via molecular dynamics (MDs) simulations and docking investigations. The results showed that the mutant ace1 has different substrate entry points and structural modifications that affect the enzyme inhibitor affinity. Significant differences in ace1 gene expression between the mutant and wild-type strains were revealed by real-time quantitative PCR, which raises the possibility of a relationship between ace1 mutations and changes in mRNA transcription levels. Plutella xylostella, a destructive crucifer pest, can rapidly develop resistance to most classes of pesticides. This study investigated the molecular resistance mechanisms to chlorpyrifos, an organophosphate pesticide. Two P. xylostella genes, ace1 and ace2, were described. The nucleotide sequence results revealed no variation in ace2, while the resistant strain (Kar-R) had four amino acid alterations in ace1, two of which (A298S and G324A) were previously shown to confer organophosphate resistance in P. xylostella. In the present study, the 3D model structures of both the wild-type (Gu-S) and mutant (Kar-R) of P. xylostella ace1 strains were studied through molecular dynamics (MDs) simulations and molecular docking. Molecular dynamics simulations of RMSD revealed less structural deviation in the ace1 mutant than in its wild-type counterpart. Higher flexibility in the 425–440 amino acid region in the mutant active site (Glu422 and Acyl pocket) increased the active site's entropy, reducing the enzyme's affinity for the inhibitors. Gene expression analysis revealed that the relative transcription levels of ace1 were significantly different in the Kar-R strain compared with the Gu-S strain. This study enhances the understanding of the mechanisms governing ace1′s resistance to insecticide and provides essential insights for new insecticides as well as valuable insights into environmentally conscious pest management techniques. [ABSTRACT FROM AUTHOR]

Copyright of Insects (2075-4450) is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)