Engdahl_2015_PLoS.One_10_e0138598

Reference

Title : Acetylcholinesterases from the Disease Vectors Aedes aegypti and Anopheles gambiae: Functional Characterization and Comparisons with Vertebrate Orthologues - Engdahl_2015_PLoS.One_10_e0138598
Author(s) : Engdahl C , Knutsson S , Fredriksson SA , Linusson A , Bucht G , Ekstrom F
Ref : PLoS ONE , 10 :e0138598 , 2015
Abstract :

Mosquitoes of the Anopheles (An.) and Aedes (Ae.) genus are principal vectors of human diseases including malaria, dengue and yellow fever. Insecticide-based vector control is an established and important way of preventing transmission of such infections. Currently used insecticides can efficiently control mosquito populations, but there are growing concerns about emerging resistance, off-target toxicity and their ability to alter ecosystems. A potential target for the development of insecticides with reduced off-target toxicity is the cholinergic enzyme acetylcholinesterase (AChE). Herein, we report cloning, baculoviral expression and functional characterization of the wild-type AChE genes (ace-1) from An. gambiae and Ae. aegypti, including a naturally occurring insecticide-resistant (G119S) mutant of An. gambiae. Using enzymatic digestion and liquid chromatography-tandem mass spectrometry we found that the secreted proteins were post-translationally modified. The Michaelis-Menten constants and turnover numbers of the mosquito enzymes were lower than those of the orthologous AChEs from Mus musculus and Homo sapiens. We also found that the G119S substitution reduced the turnover rate of substrates and the potency of selected covalent inhibitors. Furthermore, non-covalent inhibitors were less sensitive to the G119S substitution and differentiate the mosquito enzymes from corresponding vertebrate enzymes. Our findings indicate that it may be possible to develop selective non-covalent inhibitors that effectively target both the wild-type and insecticide resistant mutants of mosquito AChE.

PubMedSearch : Engdahl_2015_PLoS.One_10_e0138598
PubMedID: 26447952
Gene_locus related to this paper: aedae-ACHE1 , anoga-ACHE1

Related information

Mutation G119S_anoga-ACHE1
Gene_locus G119S_anoga-ACHE1    aedae-ACHE1    anoga-ACHE1

Citations formats

Engdahl C, Knutsson S, Fredriksson SA, Linusson A, Bucht G, Ekstrom F (2015)
Acetylcholinesterases from the Disease Vectors Aedes aegypti and Anopheles gambiae: Functional Characterization and Comparisons with Vertebrate Orthologues
PLoS ONE 10 :e0138598

Engdahl C, Knutsson S, Fredriksson SA, Linusson A, Bucht G, Ekstrom F (2015)
PLoS ONE 10 :e0138598