Discovery and Structure of a Potent and Highly Specific Blocker of Insect Calcium Channels

Xiu Hong Wang, Mark Connor, David Wilson, Harry I. Wilson, Graham M. Nicholson, Ross Smith, Denis Shaw, Joel P. Mackay, Paul F. Alewood, Macdonald J. Christie, Glenn F. King*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

69 Citations (Scopus)

Abstract

We have isolated a novel family of insect-selective neurotoxins that appear to be the most potent blockers of insect voltage-gated calcium channels reported to date. These toxins display exceptional phylogenetic specificity, with at least a 10,000-fold preference for insect versus vertebrate calcium channels. The structure of one of the toxins reveals a highly structured, disulfide-rich core and a structurally disordered C-terminal extension that is essential for channel blocking activity. Weak structural/functional homology with ω-agatoxin-IVA/B, the prototypic inhibitor of vertebrate P-type calcium channels, suggests that these two toxin families might share a similar mechanism of action despite their vastly different phylogenetic specificities.

Original languageEnglish
Pages (from-to)40306-40312
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number43
Publication statusPublished - 26 Oct 2001
Externally publishedYes

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