AA sequence: Ala-Ser-Cys3-Arg-Thr-Pro-Lys-Asp-Cys9-Ala-Asp-Pro-Cys13-Arg-Lys-Glu-Thr-Gly-Cys19-Pro-Tyr-Gly-Lys-Cys24-Met-Asn-Arg-Lys-Cys29-Lys-Cys31-Asn-Arg-Cys34-NH2
Disulfide bonds: Cys3-Cys24, Cys9-Cys29, Cys13-Cys31 and Cys19-Cys34
Length (aa): 34
Formula: C149H246N54O46S9
Molecular Weight: 3819.87 Da
Appearance: White lyophilized solid
Solubility: water and saline buffer
CAS number: not available
Source: Synthetic
Purity rate: > 95 %
HsTx1
Selective blocker of Kv1.3 channel
HsTx-1 is a member of the a-KTx6 family of scorpion toxins active on voltage-gated Kv1.3 channels (Kd close to 10 pM). HsTx-1 is also very active on Kv1.1 channels (IC50 around 7 nM). It is however inactive on apamin-sensitive SK channels. It is one of the most potent toxins active on Kv1.3 channel.
Contact us
A potent and Kv1.3-selective analogue of the scorpion toxin HsTX1 as a potential therapeutic for autoimmune diseases
HsTX1 toxin, from the scorpion Heterometrus spinnifer, is a 34-residue, C-terminally amidated peptide cross-linked by four disulfide bridges. Here we describe new HsTX1 analogues with an Ala, Phe, Val or Abu substitution at position 14. Complexes of HsTX1 with the voltage-gated potassium channels Kv1.3 and Kv1.1 were created using docking and molecular dynamics simulations, then umbrella sampling simulations were performed to construct the potential of mean force (PMF) of the ligand and calculate the corresponding binding free energy for the most stable configuration. The PMF method predicted that the R14A mutation in HsTX1 would yield a > 2 kcal/mol gain for the Kv1.3/Kv1.1 selectivity free energy relative to the wild-type peptide. Functional assays confirmed the predicted selectivity gain for HsTX1[R14A] and HsTX1[R14Abu], with an affinity for Kv1.3 in the low picomolar range and a selectivity of more than 2,000-fold for Kv1.3 over Kv1.1. This remarkable potency and selectivity for Kv1.3, which is significantly up-regulated in activated effector memory cells in humans, suggest that these analogues represent valuable leads in the development of therapeutics for autoimmune diseases.
Rashid MH, et al. (2014) A potent and Kv1.3-selective analogue of the scorpion toxin HsTX1 as a potential therapeutic for autoimmune diseases. Sci Rep. PMID: 24676092
Structural and functional consequences of the presence of a fourth disulfide bridge in the scorpion short toxins: solution structure of the potassium channel inhibitor HsTX1
Savarin, P., et al. (1999) Structural and functional consequences of the presence of a fourth disulfide bridge in the scorpion short toxins: solution structure of the potassium channel inhibitor HsTX1. Protein Sci. PMID: 10631983
A four-disulphide-bridged toxin, with high affinity towards voltage-gated K+ channels, isolated from Heterometrusspinnifer (Scorpionidae) venom
Lebrun, B., et al. (1997) A four-disulphide-bridged toxin, with high affinity towards voltage-gated K+ channels, isolated from Heterometrusspinnifer (Scorpionidae) venom. Biochem. PMID: 9359871