2i1t
From Proteopedia
(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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| - | [[Image:2i1t.gif|left|200px]]<br /><applet load="2i1t" size=" | + | [[Image:2i1t.gif|left|200px]]<br /><applet load="2i1t" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2i1t" /> | caption="2i1t" /> | ||
'''Solution structure of Jingzhaotoxin-III, a novel toxin inhibiting both Nav and Kv channels'''<br /> | '''Solution structure of Jingzhaotoxin-III, a novel toxin inhibiting both Nav and Kv channels'''<br /> | ||
==Overview== | ==Overview== | ||
| - | We have isolated a cardiotoxin, denoted jingzhaotoxin-III (JZTX-III), from | + | 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== | ==About this Structure== | ||
| - | 2I1T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Chilobrachys_jingzhao Chilobrachys jingzhao]. Full crystallographic information is available from [http:// | + | 2I1T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Chilobrachys_jingzhao Chilobrachys jingzhao]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I1T OCA]. |
==Reference== | ==Reference== | ||
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[[Category: cardiac myocytes]] | [[Category: cardiac myocytes]] | ||
[[Category: jingzhaotoxin-iii]] | [[Category: jingzhaotoxin-iii]] | ||
| - | [[Category: kv2 | + | [[Category: kv2 1 channel]] |
[[Category: nav channel]] | [[Category: nav channel]] | ||
[[Category: solution structure]] | [[Category: solution structure]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:48:16 2008'' |
Revision as of 15:48, 21 February 2008
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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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