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

doi:10.1074/jbc.M105206200

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 journal › Article › peer-review

73 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 language	English
Pages (from-to)	40306-40312
Number of pages	7
Journal	Journal of Biological Chemistry
Volume	276
Issue number	43
DOIs	https://doi.org/10.1074/jbc.M105206200
Publication status	Published - 26 Oct 2001

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title = "Discovery and Structure of a Potent and Highly Specific Blocker of Insect Calcium Channels",

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.",

author = "Wang, \{Xiu Hong\} and Mark Connor and David Wilson and Wilson, \{Harry I.\} and Nicholson, \{Graham M.\} and Ross Smith and Denis Shaw and Mackay, \{Joel P.\} and Alewood, \{Paul F.\} and Christie, \{Macdonald J.\} and King, \{Glenn F.\}",

year = "2001",

month = oct,

day = "26",

doi = "10.1074/jbc.M105206200",

language = "English",

volume = "276",

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journal = "Journal of Biological Chemistry",

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TY - JOUR

T1 - Discovery and Structure of a Potent and Highly Specific Blocker of Insect Calcium Channels

AU - Wang, Xiu Hong

AU - Connor, Mark

AU - Wilson, David

AU - Wilson, Harry I.

AU - Nicholson, Graham M.

AU - Smith, Ross

AU - Shaw, Denis

AU - Mackay, Joel P.

AU - Alewood, Paul F.

AU - Christie, Macdonald J.

AU - King, Glenn F.

PY - 2001/10/26

Y1 - 2001/10/26

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/0035955737

U2 - 10.1074/jbc.M105206200

DO - 10.1074/jbc.M105206200

M3 - Article

SN - 0021-9258

VL - 276

SP - 40306

EP - 40312

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 43

ER -

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

Abstract

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