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PMID: 10881200 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Discovery and characterization of a family of insecticidal neurotoxins with a rare vicinal disulfide bridge.

Nature structural biology ·Vol. 7 ·No. 6 ·2000-06-00 ·Pages 505-13

Wang X, Connor M, Smith R, Maciejewski MW, Howden ME, Nicholson GM, Christie MJ, King GF

Abstract

We have isolated a family of insect-selective neurotoxins from the venom of the Australian funnel-web spider that appear to be good candidates for biopesticide engineering. These peptides, which we have named the Janus-faced atracotoxins (J-ACTXs), each contain 36 or 37 residues, with four disulfide bridges, and they show no homology to any sequences in the protein/DNA databases. The three-dimensional structure of one of these toxins reveals an extremely rare vicinal disulfide bridge that we demonstrate to be critical for insecticidal activity. We propose that J-ACTX comprises an ancestral protein fold that we refer to as the disulfide-directed beta-hairpin.

MeSH Terms

Amino Acid Motifs Amino Acid Sequence Animals Binding Sites Chromatography, High Pressure Liquid Disulfides/chemistry,metabolism Evolution, Molecular Insecta/cytology,drug effects,metabolism Insecticides/chemistry,isolation & purification,toxicity Lethal Dose 50 Mice Models, Molecular Molecular Sequence Data Neurons/drug effects,metabolism Neurotoxins/chemistry,isolation & purification,toxicity Nuclear Magnetic Resonance, Biomolecular Protein Folding Protein Structure, Secondary Protein Structure, Tertiary Receptors, Cholinergic/metabolism Sequence Alignment Species Specificity Spider Venoms/chemistry

Chemicals

Disulfides Insecticides Neurotoxins Receptors, Cholinergic Spider Venoms

Authors & Affiliations

8 authors, click to expand affiliations / ORCID

Wang X

Department of Biochemistry, University of Connecticut Health Center, Farmington 06032, USA.

Connor M

Smith R

Maciejewski M W

Howden M E

Nicholson G M

Christie M J

King G F

Article Info

Journal

Nature structural biology

Abbr.

Nat Struct Biol

ISSN

1072-8368

DOI

10.1038/75921

Published

2000-06-00

Pages

505-13

Language

English

Region

United States

NLM ID

9421566

Subset

Databases

PDB

1DL0

External Links

PubMed source DOI: 10.1038/75921

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Discovery and characterization of a family of insecticidal neurotoxins with a rare vicinal disulfide bridge.

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