Irditoxin, a novel covalently linked heterodimeric three-finger toxin with high taxon-specific neurotoxicity

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Title Irditoxin, a novel covalently linked heterodimeric three-finger toxin with high taxon-specific neurotoxicity
Author Pawlak, Joanna; Mackessy, Stephen P.; Sixberry, Nicole M.; Stura, Enrico A.; Du, Marie Helene Le; Menez, Renee; Foo, Chun Shin; Menez, Andre; Nirthanan, S. Niru; Kini, R. Manjunatha
Journal Name The FASEB Journal
Year Published 2009
Place of publication United States
Publisher Federation of American Societies for Experimental Biology
Abstract A novel heterodimeric three-finger neurotoxin, irditoxin, was isolated from venom of the brown treesnake Boiga irregularis (Colubridae). Irditoxin subunit amino acid sequences were determined by Edman degradation and cDNA sequencing. The crystal structure revealed two subunits with a three-finger protein fold, typical for "nonconventional" toxins such as denmotoxin, bucandin, and candoxin. This is the first colubrid three-finger toxin dimer, covalently connected via an interchain disulfide bond. Irditoxin showed taxon-specific lethality toward birds and lizards and was nontoxic toward mice. It produced a potent neuromuscular blockade at the avian neuromuscular junction (IC(50)=10 nM), comparable to alpha-bungarotoxin, but was three orders of magnitude less effective at the mammalian neuromuscular junction. Covalently linked heterodimeric three-finger toxins found in colubrid venoms constitute a new class of venom peptides, which may be a useful source of new neurobiology probes and therapeutic leads.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1096/fj.08-113555
Copyright Statement Copyright 2009 Federation of American Societies for Experimental Biology. Self-archiving of the author-manuscript version is not yet supported by this publisher. Please refer to the journal link for access to the definitive, published version or contact the authors for more information.
Volume 23
Issue Number 2
Page from 534
Page to 545
ISSN 0892-6638
Date Accessioned 2009-07-09
Date Available 2010-09-27T06:53:42Z
Language en_AU
Research Centre Griffith Health Institute
Faculty Griffith Health Faculty
Subject Basic Pharmacology; Toxicology (incl Clinical Toxicology)
URI http://hdl.handle.net/10072/34242
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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