Novel acetylcholinesterase target site for malaria mosquito control

Research output: Contribution to journalArticle

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Abstract

Current anticholinesterase pesticides were developed during World War II and are toxic to mammals because they target a catalytic serine residue of acetylcholinesterases (AChEs) in insects and in mammals. A sequence analysis of AChEs from 73 species and a three-dimensional model of a malaria-carrying mosquito (Anopheles gambiae) AChE (AgAChE) reported here show that C286 and R339 of AgAChE are conserved at the opening of the active site of AChEs in 17 invertebrate and four insect species, respectively. Both residues are absent in the active site of AChEs of human, monkey, dog, cat, cattle, rabbit, rat, and mouse. The 17 invertebrates include house mosquito, Japanese encephalitis mosquito, African malaria mosquito, German cockroach, Florida lancelet, rice leaf beetle, African bollworm, beet armyworm, codling moth, diamondback moth, domestic silkworm, honey bee, oat or wheat aphid, the greenbug, melon or cotton aphid, green peach aphid, and English grain aphid. The four insects are house mosquito, Japanese encephalitis mosquito, African malaria mosquito, and German cockroach. The discovery of the two invertebrate-specific residues enables the development of effective and safer pesticides that target the residues present only in mosquito AChEs rather than the ubiquitous serine residue, thus potentially offering an effective control of mosquito-borne malaria. Anti- AgAChE pesticides can be designed to interact with R339 and subsequently covalently bond to C286. Such pesticides would be toxic to mosquitoes but not to mammals.

Original languageEnglish (US)
Article numbere58
JournalPLoS One
Volume1
Issue number1
DOIs
StatePublished - Dec 20 2006

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Mosquito control
Mosquito Control
mosquito control
Acetylcholinesterase
acetylcholinesterase
Culicidae
malaria
Malaria
Pesticides
Mammals
Anopheles gambiae
Aphids
Poisons
Serine
pesticides
Invertebrates
Blattellidae
Japanese Encephalitis
Insects
Blattella germanica

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Novel acetylcholinesterase target site for malaria mosquito control. / Pang, Yuan-Ping.

In: PLoS One, Vol. 1, No. 1, e58, 20.12.2006.

Research output: Contribution to journalArticle

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