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| - | [[Image:2i1t.gif|left|200px]] | + | [[Image:2i1t.png|left|200px]] |
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| | {{STRUCTURE_2i1t| PDB=2i1t | SCENE= }} | | {{STRUCTURE_2i1t| PDB=2i1t | SCENE= }} |
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| - | '''Solution structure of Jingzhaotoxin-III, a novel toxin inhibiting both Nav and Kv channels'''
| + | ===Solution structure of Jingzhaotoxin-III, a novel toxin inhibiting both Nav and Kv channels=== |
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| - | | + | {{ABSTRACT_PUBMED_15084603}} |
| - | ==Overview==
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| - | 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.
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| | ==About this Structure== | | ==About this Structure== |
| - | 2I1T is a [[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].
| + | [[2i1t]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Chilobrachys_guangxiensis Chilobrachys guangxiensis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I1T OCA]. |
| - | | + | [[Category: Chilobrachys guangxiensis]] |
| - | ==Reference==
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| - | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15084603 15084603]
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| - | [[Category: Chilobrachys jingzhao]] | + | |
| - | [[Category: Single protein]]
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| | [[Category: Liang, S.]] | | [[Category: Liang, S.]] |
| | [[Category: Liao, Z.]] | | [[Category: Liao, Z.]] |
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| | [[Category: Nav channel]] | | [[Category: Nav channel]] |
| | [[Category: Solution structure]] | | [[Category: Solution structure]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:58:33 2008''
| + | [[Category: Toxin]] |
