title: A butterfly effect: highly insecticidal resistance caused by only a conservative residue mutated of drosophila melanogaster acetylcholinesterase.
abstract: Acetylcholinesterase (AChE) and its mutation recently emerged as a significant research area, due to its resistance against organophosphate and carbamate insecticides. Residue G265, which is always a conservative residue, mutated to A265 is the most frequent mutant of AChE in Drosophila populations. However, only this mutation caused a 'butterfly effect' that gives high insecticidal resistance. Herein, the models of sensitive strain (Dm-S) and the resistance strain (Dm-R) were constructed, to give a total of 2000 ps molecular dynamics simulation and to reveal the insecticidal resistance mechanism, with implied, the active gorge of Dm-R was much less flexible than that of Dm-S. The "back door" channel was widened to accelerate the detoxication against insecticides by the conformation changing of W83 and I161. All the distances (S238-H480, S238-G150, S238-G151, Y71-M153) in Dm-R became smaller than those in Dm-S, which may deeply influence the binding between the insecticides and DmAChE.
authors.affiliation: East China University of Science and Technology, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Fan
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: You
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.forename: Jiagao
authors.initials: J
authors.lastname: Cheng
authors.forename: Yun
authors.initials: Y
authors.lastname: Tang
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Tang
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics*; D000818:Animals; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D007305:Insecticide Resistance / Q000235:genetics*; D056004:Molecular Dynamics Simulation; D020125:Mutation, Missense; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D000110:Acetylcholinesterase