2i1t
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(New page: 200px<br /><applet load="2i1t" size="450" color="white" frame="true" align="right" spinBox="true" caption="2i1t" /> '''Solution structure of Jingzhaotoxin-III, a n...)
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Revision as of 09:59, 21 November 2007
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Solution structure of Jingzhaotoxin-III, a novel toxin inhibiting both Nav and Kv channels
Overview
We have isolated a cardiotoxin, denoted jingzhaotoxin-III (JZTX-III), from, the venom of the Chinese spider Chilobrachys jingzhao. The toxin contains, 36 residues stabilized by three intracellular disulfide bridges (I-IV, II-V, and III-VI), assigned by a chemical strategy of partial reduction, and sequence analysis. Cloned and sequenced using 3'-rapid amplification, of cDNA ends and 5'-rapid amplification of cDNA ends, the full-length cDNA, encoded a 63-residue precursor of JZTX-III. Different from other spider, peptides, it contains an uncommon endoproteolytic site (-X-Ser-) anterior, to mature protein and the intervening regions of 5 residues, which is the, smallest in spider toxin cDNAs identified to date. Under whole cell, recording, JZTX-III showed no effects on voltage-gated sodium channels, (VGSCs) or calcium channels in dorsal root ganglion neurons, whereas it, significantly inhibited tetrodotoxin-resistant VGSCs with an IC(50) value, of 0.38 microm in rat cardiac myocytes. Different from scorpion, beta-toxins, it caused a 10-mV depolarizing shift in the channel, activation threshold. The binding site for JZTX-III on VGSCs is further, suggested to be site 4 with a simple competitive assay, which at 10 microm, eliminated the slowing currents induced by Buthus martensi Karsch I, (BMK-I, scorpion alpha-like toxin) completely. JZTX-III shows higher, selectivity for VGSC isoforms than other spider toxins affecting VGSCs, and the toxin hopefully represents an important ligand for discriminating, cardiac VGSC subtype.
About this Structure
2I1T is a Single protein structure of sequence from Chilobrachys jingzhao. Full crystallographic information is available from OCA.
Reference
Jingzhaotoxin-III, a novel spider toxin inhibiting activation of voltage-gated sodium channel in rat cardiac myocytes., Xiao Y, Tang J, Yang Y, Wang M, Hu W, Xie J, Zeng X, Liang S, J Biol Chem. 2004 Jun 18;279(25):26220-6. Epub 2004 Apr 14. PMID:15084603
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