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

2001; Elsevier BV; Volume: 276; Issue: 43 Linguagem: Inglês

10.1074/jbc.m105206200

1083-351X

Xiuhong Wang, Mark Connor, David T. Wilson, Harry Wilson, Graham M. Nicholson, Ross Smith, Denis C. Shaw, Joel P. Mackay, Paul F. Alewood, MacDonald J. Christie, Glenn F. King,

Venomous Animal Envenomation and Studies

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.