Discovery and structure of a potent and highly specific blocker of insect calcium channels

Wang, Xiu-Hong, Connor, Mark, Wilson, David, Wilson, Harry I., Nicholson, Graham M., Smith, Ross, Shaw, Denis, Mackay, Joel P., Alewood, Paul, Christie, Macdonald J., and King, Glenn F. (2001) Discovery and structure of a potent and highly specific blocker of insect calcium channels. Journal of Biological Chemistry, 276 (43). pp. 40306-40312.

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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.

Item ID: 39016
Item Type: Article (Research - C1)
ISSN: 1083-351X
Date Deposited: 03 Dec 2015 04:20
FoR Codes: 03 CHEMICAL SCIENCES > 0304 Medicinal and Biomolecular Chemistry > 030406 Proteins and Peptides @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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