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2m4x

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==Analysis of the structural and molecular basis of voltage-sensitive sodium channel inhibition by the spider toxin, Huwentoxin-IV (-TRTX-Hh2a).==
==Analysis of the structural and molecular basis of voltage-sensitive sodium channel inhibition by the spider toxin, Huwentoxin-IV (-TRTX-Hh2a).==
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<StructureSection load='2m4x' size='340' side='right' caption='[[2m4x]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
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<StructureSection load='2m4x' size='340' side='right'caption='[[2m4x]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[2m4x]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Chinese_bird_spider Chinese bird spider]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M4X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2M4X FirstGlance]. <br>
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<table><tr><td colspan='2'>[[2m4x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cyriopagopus_schmidti Cyriopagopus schmidti]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M4X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M4X FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2m4z|2m4z]], [[2m50|2m50]]</td></tr>
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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=2m4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m4x OCA], [https://pdbe.org/2m4x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m4x RCSB], [https://www.ebi.ac.uk/pdbsum/2m4x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m4x ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2m4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m4x OCA], [http://pdbe.org/2m4x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2m4x RCSB], [http://www.ebi.ac.uk/pdbsum/2m4x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2m4x ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/TXH4_HAPSC TXH4_HAPSC]] This lethal neurotoxin acts selectively on tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channels (Nav), with an IC(50) of 30 nM in rat DRG neurons. Preferentially inhibits neuronal voltage-gated sodium channel subtype hNav1.7/SCN9A (IC(50) is 26 nM), rNav1.2/SCN2A (IC(50) is 150 nM), and rNav1.3/SCN3A (IC(50) is 338 nM), compared with muscle subtypes rNav1.4/SCN4A and hNav1.5/SCN5A (IC(50) is > 10 uM). Inhibits activation of sodium channel by trapping the voltage sensor of domain II of the site 4 in the inward, closed configuration.<ref>PMID:12228241</ref> <ref>PMID:18628201</ref>
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[https://www.uniprot.org/uniprot/TXH4_CYRSC TXH4_CYRSC] This lethal neurotoxin (without cyclization at position 53) inhibits neuronal voltage-gated sodium channel Nav1.2/SCN2A (IC(50)=10-150 nM), rNav1.3/SCN3A (IC(50)=338 nM), Nav1.6/SCN8A (IC(50)=117 nM), and hNav1.7/SCN9A (IC(50)=9.6-33 nM) (PubMed:18628201, PubMed:20855463, PubMed:25658507, PubMed:29703751,PubMed:31234412, PubMed:23760503). It inhibits activation of sodium channel by trapping the voltage sensor of domain II (DIIS4) in the closed configuration (PubMed:18628201, PubMed:23760503). The toxin neither shifts the Nav1.7/SCN9A activation curve nor modifies the slope factor (PubMed:20855463). It does not slow fast-inactivation of hNav1.7/SCN9A channels (PubMed:20855463). In addition, it has only a weak affinity for lipid membranes (PubMed:18054060, PubMed:29703751, PubMed:28115115). This toxin also exists with a pyroglutamate at position 53 (PubMed:23826086). The sole difference observed between modified (mHwTx-IV) and unmodified toxins is that moderate or high depolarization voltages (200 mV) permit the unmodified toxin to dissociate, whereas mHwTx-IV toxin does not dissociate, even at high depolarization voltages (PubMed:23826086). These data indicate that mHwTx-IV strongly binds to voltage sensor of sodium channel even at extreme depolarization voltages (PubMed:23826086).<ref>PMID:12228241</ref> <ref>PMID:18054060</ref> <ref>PMID:18628201</ref> <ref>PMID:20855463</ref> <ref>PMID:21659528</ref> <ref>PMID:23523779</ref> <ref>PMID:23760503</ref> <ref>PMID:25658507</ref> <ref>PMID:28115115</ref> <ref>PMID:29483648</ref>
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== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Chinese bird spider]]
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[[Category: Cyriopagopus schmidti]]
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[[Category: Flinspach, M]]
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[[Category: Large Structures]]
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[[Category: Gibbs, A]]
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[[Category: Flinspach M]]
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[[Category: Toxin]]
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[[Category: Gibbs A]]
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[[Category: Venom]]
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Current revision

Analysis of the structural and molecular basis of voltage-sensitive sodium channel inhibition by the spider toxin, Huwentoxin-IV (-TRTX-Hh2a).

PDB ID 2m4x

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