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2i1t

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[[Image:2i1t.gif|left|200px]]<br /><applet load="2i1t" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2i1t" />
 
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'''Solution structure of Jingzhaotoxin-III, a novel toxin inhibiting both Nav and Kv channels'''<br />
 
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==Overview==
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==Solution structure of Jingzhaotoxin-III, a novel toxin inhibiting both Nav and Kv channels==
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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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<StructureSection load='2i1t' size='340' side='right'caption='[[2i1t]]' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[2i1t]] is a 1 chain structure with sequence from [https://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]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I1T FirstGlance]. <br>
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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].
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2i1t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i1t OCA], [https://pdbe.org/2i1t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i1t RCSB], [https://www.ebi.ac.uk/pdbsum/2i1t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i1t ProSAT]</span></td></tr>
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==Reference==
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</table>
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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://ispc.weizmann.ac.il//pmbin/getpm?pmid=15084603 15084603]
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== Function ==
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[[Category: Chilobrachys jingzhao]]
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[https://www.uniprot.org/uniprot/JZTX3_CHIGU JZTX3_CHIGU] Selectively inhibits activation of voltage-gated sodium channels (VGSC) (Nav1.5/SCN5A) in rat cardiac myocytes, followed by shifting activated voltage in a depolarizing direction. The binding site on VGSC is suggested to be site 4 located at the extracellular S3-S4 loop of the channel. Also binds to voltage-gated potassium channels (Kv2.1/KCNB1).<ref>PMID:17150181</ref>
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[[Category: Single protein]]
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== References ==
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[[Category: Liang, S.]]
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<references/>
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[[Category: Liao, Z.]]
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__TOC__
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[[Category: Peng, K.]]
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</StructureSection>
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[[Category: cardiac myocytes]]
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[[Category: Chilobrachys guangxiensis]]
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[[Category: jingzhaotoxin-iii]]
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[[Category: Large Structures]]
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[[Category: kv2 1 channel]]
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[[Category: Liang S]]
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[[Category: nav channel]]
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[[Category: Liao Z]]
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[[Category: solution structure]]
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[[Category: Peng K]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:48:16 2008''
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Current revision

Solution structure of Jingzhaotoxin-III, a novel toxin inhibiting both Nav and Kv channels

PDB ID 2i1t

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