This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


2m4x

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (09:27, 14 June 2023) (edit) (undo)
 
(3 intermediate revisions not shown.)
Line 1: Line 1:
 +
==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).==
-
<StructureSection load='2m4x' size='340' side='right' caption='[[2m4x]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+
<StructureSection load='2m4x' size='340' side='right'caption='[[2m4x]]' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<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>
+
<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>
-
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2m4z|2m4z]], [[2m50|2m50]]</td></tr>
+
</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>
-
<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]</span></td></tr>
+
</table>
</table>
== Function ==
== Function ==
-
[[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>
+
[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>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
Line 21: Line 21:
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Chinese bird spider]]
+
[[Category: Cyriopagopus schmidti]]
-
[[Category: Flinspach, M]]
+
[[Category: Large Structures]]
-
[[Category: Gibbs, A]]
+
[[Category: Flinspach M]]
-
[[Category: Toxin]]
+
[[Category: Gibbs A]]
-
[[Category: Venom]]
+

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

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2m4x"
Personal tools