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

Wang, Xiu-hong; Connor, Mark; Wilson, David; Wilson, Harry; Nicholson, Graham; Smith, Ross; Shaw, Denis; Mackay, Joel Peter; Alewood, Paul F; Christie, Macdonald J; King, Glenn

Description

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...[Show more]

dc.contributor.authorWang, Xiu-hong
dc.contributor.authorConnor, Mark
dc.contributor.authorWilson, David
dc.contributor.authorWilson, Harry
dc.contributor.authorNicholson, Graham
dc.contributor.authorSmith, Ross
dc.contributor.authorShaw, Denis
dc.contributor.authorMackay, Joel Peter
dc.contributor.authorAlewood, Paul F
dc.contributor.authorChristie, Macdonald J
dc.contributor.authorKing, Glenn
dc.date.accessioned2015-12-13T23:26:24Z
dc.identifier.issn0021-9258
dc.identifier.urihttp://hdl.handle.net/1885/92818
dc.description.abstractWe 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.
dc.publisherAmerican Society for Biochemistry and Molecular Biology Inc
dc.sourceJournal of Biological Chemistry
dc.subjectKeywords: calcium channel blocking agent; insecticide; neurotoxin; omega agatoxin IVA; omega atracotoxin Hv2a; omega-atracotoxin Hv2a; protein precursor; recombinant protein; spider venom; calcium channel; calcium channel P type; amino acid sequence; animal; articl
dc.titleDiscovery and structure of a potent and highly specific blocker of insect calcuim channels
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume276
dc.date.issued2001
local.identifier.absfor060808 - Invertebrate Biology
local.identifier.ariespublicationMigratedxPub26050
local.type.statusPublished Version
local.contributor.affiliationWang, Xiu-hong, University of Connecticut
local.contributor.affiliationConnor, Mark, University of Sydney
local.contributor.affiliationWilson, David, University of Technology Sydney
local.contributor.affiliationWilson, Harry, University of Technology Sydney
local.contributor.affiliationNicholson, Graham, University of Technology Sydney
local.contributor.affiliationSmith, Ross, NSW Rural Fire Service
local.contributor.affiliationShaw, Denis, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationMackay, Joel Peter, University of Sydney
local.contributor.affiliationAlewood, Paul F, University of Queensland
local.contributor.affiliationChristie, Macdonald J, University of Sydney
local.contributor.affiliationKing, Glenn, University of Connecticut
local.description.embargo2037-12-31
local.bibliographicCitation.issue43
local.bibliographicCitation.startpage40306
local.bibliographicCitation.lastpage40312
dc.date.updated2015-12-12T09:46:29Z
local.identifier.scopusID2-s2.0-0035955737
CollectionsANU Research Publications

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