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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== |
| - | <StructureSection load='2i1t' size='340' side='right'caption='[[2i1t]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2i1t' size='340' side='right'caption='[[2i1t]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2i1t]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Chilobrachys_jingzhao Chilobrachys jingzhao]. 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 [http://proteopedia.org/fgij/fg.htm?mol=2I1T FirstGlance]. <br> | + | <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> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2i1t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i1t OCA], [http://pdbe.org/2i1t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2i1t RCSB], [http://www.ebi.ac.uk/pdbsum/2i1t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2i1t ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> |
| | + | <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> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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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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| - | 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<ref>PMID:15084603</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 2i1t" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Chilobrachys jingzhao]] | + | [[Category: Chilobrachys guangxiensis]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Liang, S]] | + | [[Category: Liang S]] |
| - | [[Category: Liao, Z]] | + | [[Category: Liao Z]] |
| - | [[Category: Peng, K]] | + | [[Category: Peng K]] |
| - | [[Category: Cardiac myocyte]]
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| - | [[Category: Jingzhaotoxin-iii]]
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| - | [[Category: Kv2 1 channel]]
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| - | [[Category: Nav channel]]
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| - | [[Category: Solution structure]]
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| - | [[Category: Toxin]]
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