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TTX-S selective blocker

Huwentoxin IV (HwTx-IV) is a neurotoxin that was originally isolated from Haplopelma schmidti (Chinese bird spider). This lethal neurotoxin acts selectively on tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channels, with an IC50 of 30 nM in rat DRG neurons. It preferentially inhibits neuronal voltage-gated sodium channel subtype hNav1.7 (SCN9A, IC50 is 26 nM), rNav1.2 (SCN2A, IC50 is 150 nM), and rNav1.3 (SCN3A, IC50 is 338 nM), compared with muscle subtypes rNav1.4 (SCN4A) and hNav1.5 (SCN5A) (IC50 is > 10 µM). Huwentoxin IV inhibits the activation of sodium channels by trapping the voltage sensor of domain II of the site 4 in the inward, closed configuration. Cy5-Huwentoxin IV is a fluorescently tagged version of Huwentoxin IV.

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AA sequence: Glu-Cys2-Leu-Glu-Ile-Phe-Lys-Ala-Cys9-Asn-Pro-Ser-Asn-Asp-Gln-Cys16-Cys17-Lys-Ser-Ser-Lys-Leu-Val-Cys24-Ser-Arg-Lys-Thr-Arg-Trp-Cys31-Lys-Tyr-Gln-Ile-NH2
Disulfide bonds: Cys2-Cys17, Cys9-Cys24 and Cys16-Cys31
Length (aa): 35
Formula of HwTx-IV: C174H277N51O52S6
Molecular Weight of HwTx-IV: 4107.20 Da
Appearance: dark lyophilized solid
Solubility: water and saline buffer
CAS number:
Source: Synthetic
Purity rate: > 95 %
Cy5: λex 646nm , λem 662nm
Stoichiometry: 1:1

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

Common molecular determinants of tarantula huwentoxin-IV inhibition of Na+ channel voltage sensors in domains II and IV

The tarantula toxins ProTx-II and huwentoxin-IV differentially interact with human Nav1.7 voltage sensors to inhibit channel activation and inactivation

Mechanism of action of two insect toxins huwentoxin-III and hainantoxin-VI on voltage-gated sodium channels

Tarantula huwentoxin-IV inhibits neuronal sodium channels by binding to receptor site 4 and trapping the domain ii voltage sensor in the closed configuration

Function and solution structure of huwentoxin-IV, a potent neuronal tetrodotoxin (TTX)-sensitive sodium channel antagonist from Chinese bird spider Selenocosmia huwena

Smartox's citation : A natural point mutation changes both target selectivity and mechanism of action of sea anemone toxins

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