title: An amino acid substitution attributable to insecticide-insensitivity of acetylcholinesterase in a Japanese encephalitis vector mosquito, Culex tritaeniorhynchus.
abstract: A cDNA sequence encoding a Drosophila Ace-paralogous acetylcholinesterase (AChE) precursor of 701 amino acid residues was identified as the second AChE gene (Ace2) transcript from Culex tritaeniorhynchus. The Ace2 gene is tightly linked to organophosphorus insecticide (OP)-insensitivity of AChE on chromosome 2. The cDNA sequences were compared between an insecticide-susceptible strain and the resistant strain, TYM, that exhibits a 870-fold decrease in fenitroxon-sensitivity of AChE. Two amino acid substitutions were present in TYM mosquitoes. One is F455W whose homologous position in Torped AChE (Phe331) is located in the vicinity of the catalytic His in the acyl pocket of the active site gorge. The other substitution is located to a C-terminal Ile697 position that apparently seems to be excluded from the mature protein and is irrelevant to catalytic activity. The F455W replacement in the Ace2 gene is solely responsible for the insecticide-insensitivity of AChE in TYM mosquitoes.
authors.affiliation: Institute of Agriculture and Forestry, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nabeshima
authors.forename: Akio
authors.initials: A
authors.lastname: Mori
authors.forename: Toshinori
authors.initials: T
authors.lastname: Kozaki
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Iwata
authors.forename: Osamu
authors.initials: O
authors.lastname: Hidoh
authors.forename: Shizuko
authors.initials: S
authors.lastname: Harada
authors.forename: Shinji
authors.initials: S
authors.lastname: Kasai
authors.forename: David W
authors.initials: DW
authors.lastname: Severson
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kono
authors.forename: Takashi
authors.initials: T
authors.lastname: Tomita
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D002874:Chromosome Mapping; D003465:Culex; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004672:Encephalitis, Japanese / Q000635:transmission*; D005278:Fenitrothion / Q000031:analogs & derivatives* / Q000494:pharmacology; D008040:Genetic Linkage; D006639:Histidine / Q000737:chemistry; D007305:Insecticide Resistance; D007306:Insecticides / Q000494:pharmacology*; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D002800:Cholinesterase Inhibitors; D018076:DNA, Complementary; D007306:Insecticides; D012333:RNA, Messenger; C007711:fenitrooxone; D006639:Histidine; D000110:Acetylcholinesterase; D005278:Fenitrothion