Selective and irreversible inhibitors of aphid acetylcholinesterases: Steps toward human-safe insecticides

Yuan-Ping Pang, Sanjay K. Singh, Yang Gao, T. Leon Lassiter, Rajesh K. Mishra, Kun Yan Zhu, William Stephen Brimijoin

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Aphids, among the most destructive insects to world agriculture, are mainly controlled by organophosphate insecticides that disable the catalytic serine residue of acetylcholinesterase (AChE). Because these agents also affect vertebrate AChEs, they are toxic to non-target species including humans and birds. We previously reported that a cysteine residue (Cys), found at the AChE active site in aphids and other insects but not mammals, might serve as a target for insect-selective pesticides. However, aphids have two different AChEs (termed AP and AO), and only AP-AChE carries the unique Cys. The absence of the active-site Cys in AO-AChE might raise concerns about the utility of targeting that residue. Herein we report the development of a methanethiosulfonate-containing small molecule that, at 6.0 μM, irreversibly inhibits 99% of all AChE activity extracted from the greenbug aphid (Schizaphis graminum) without any measurable inhibition of the human AChE. Reactivation studies using b-mercaptoethanol confirm that the irreversible inhibition resulted from the conjugation of the inhibitor to the unique Cys. These results suggest that AO-AChE does not contribute significantly to the overall AChE activity in aphids, thus offering new insight into the relative functional importance of the two insect AChEs. More importantly, by demonstrating that the Cystargeting inhibitor can abolish AChE activity in aphids, we can conclude that the unique Cys may be a viable target for speciesselective agents to control aphids without causing human toxicity and resistance problems.

Original languageEnglish (US)
Article numbere4349
JournalPLoS One
Volume4
Issue number2
DOIs
StatePublished - 2009

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Aphids
Cholinesterase Inhibitors
Acetylcholinesterase
acetylcholinesterase
Insecticides
Aphidoidea
insecticides
Insects
Schizaphis graminum
insects
active sites
Pain
Catalytic Domain
Mammals
organophosphorus insecticides
Organophosphates
Mercaptoethanol
Poisons
nontarget organisms
Birds

ASJC Scopus subject areas

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

Cite this

Selective and irreversible inhibitors of aphid acetylcholinesterases : Steps toward human-safe insecticides. / Pang, Yuan-Ping; Singh, Sanjay K.; Gao, Yang; Lassiter, T. Leon; Mishra, Rajesh K.; Zhu, Kun Yan; Brimijoin, William Stephen.

In: PLoS One, Vol. 4, No. 2, e4349, 2009.

Research output: Contribution to journalArticle

Pang, Yuan-Ping ; Singh, Sanjay K. ; Gao, Yang ; Lassiter, T. Leon ; Mishra, Rajesh K. ; Zhu, Kun Yan ; Brimijoin, William Stephen. / Selective and irreversible inhibitors of aphid acetylcholinesterases : Steps toward human-safe insecticides. In: PLoS One. 2009 ; Vol. 4, No. 2.
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