2i1t

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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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<StructureSection load='2i1t' size='340' side='right'caption='[[2i1t]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
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<StructureSection load='2i1t' size='340' side='right'caption='[[2i1t]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[2i1t]] is a 1 chain structure with sequence from [https://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 [https://proteopedia.org/fgij/fg.htm?mol=2I1T FirstGlance]. <br>
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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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</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>
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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>
</table>
</table>
== Function ==
== Function ==
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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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[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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<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&reg;/PubMed&reg;, 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>
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[[Category: Chilobrachys jingzhao]]
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[[Category: Chilobrachys guangxiensis]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Liang, S]]
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[[Category: Liang S]]
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[[Category: Liao, Z]]
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[[Category: Liao Z]]
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[[Category: Peng, K]]
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[[Category: Peng K]]
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[[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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Revision as of 16:37, 13 December 2023

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

PDB ID 2i1t

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