Peptide Information

General Information of This Peptide
Peptide ID
BTDP006532
Peptide Name
Huwentoxin-IV
Symonym
Huwentoxin-4; Huwentoxin-IVa; Huwentoxin-IVb; Huwentoxin-IVc; Mu-theraphotoxin-Hs2a
Species
Cyriopagopus schmidti (Chinese bird spider) (Haplopelma schmidti)
Uniprot Name
TXH4_CYRSC
Alphafold ID
P83303
3D Structure
Download
2D Sequence
3D Structure
Source
RSCB PDB: 1MB6
Sequence
MVNMKASMFLALAGLVLLFVVCYASESEEKEFSNELLSSVLAVDDNSKGEERECLEIFKA
CNPSNDQCCKSSKLVCSRKTRWCKYQIGK
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Sequence Length
89
Mass (Da)
9997
Signal Sequence
MVNMKASMFLTFAGLVLLFVACYA
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Sequence Removed Signal Peptide
SESEEKEFSNELLSSVLAVDDNSKGEERECLEIFKACNPSNDQCCKSSKLVCSRKTRWCK
YQIGK
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Disulfide Bond
54-69;61-76;68-83
PDB ID
1MB6 , 2M4X , 2M4Z , 2M50 , 5T3M , 5TLR , 6W6O , 7K48
        Click to Show/Hide the Complete Species Lineage
Kingdom: Metazoa
Phylum: Arthropoda
Class: Arachnida
Order: Araneae
Family: Theraphosidae
Genus: Cyriopagopus
Species: Cyriopagopus schmidti
Full List of Activity Data of This Peptide Toxin
                        Target Name Activity Data Type Activity Data Concentration Note Reference
 Target Info    Nav1.7 IC50
9.6 - 33 nM
 . . [1- 17]
 Target Info    Nav1.2 IC50
10 - 150 nM
 . . [1- 17]
 Target Info    Nav1.6 IC50
117 nM
 . . [1- 17]
 Target Info    Nav1.3 IC50
338 nM
 . . [1- 17]
 Target Info    Nav1.5 IC50
≥10 - 25 μM
 . . [1- 17]
 Target Info    Nav1.4 IC50
3.9 - >10 μM
 . . [1- 17]
References
Ref 1 cDNA sequence analysis of seven peptide toxins from the spider Selenocosmia huwena. Toxicon. 2003 Dec;42(7):715-23. doi: 10.1016/j.toxicon.2003.08.007.
Ref 2 Molecular diversification based on analysis of expressed sequence tags from the venom glands of the Chinese bird spider Ornithoctonus huwena. Toxicon. 2008 Jun 15;51(8):1479-89. doi: 10.1016/j.toxicon.2008.03.024. Epub 2008 Mar 27.
Ref 3 Function and solution structure of huwentoxin-IV, a potent neuronal tetrodotoxin (TTX)-sensitive sodium channel antagonist from Chinese bird spider Selenocosmia huwena. J Biol Chem. 2002 Dec 6;277(49):47564-71. doi: 10.1074/jbc.M204063200. Epub 2002 Sep 11.
Ref 4 Native pyroglutamation of huwentoxin-IV: a post-translational modification that increases the trapping ability to the sodium channel. PLoS One. 2013 Jun 24;8(6):e65984. doi: 10.1371/journal.pone.0065984. Print 2013.
Ref 5 Tarantula huwentoxin-IV inhibits neuronal sodium channels by binding to receptor site 4 and trapping the domain ii voltage sensor in the closed configuration. J Biol Chem. 2008 Oct 3;283(40):27300-13. doi: 10.1074/jbc.M708447200. Epub 2008 Jul 14.
Ref 6 Synthesis and characterization of huwentoxin-IV, a neurotoxin inhibiting central neuronal sodium channels. Toxicon. 2008 Feb;51(2):230-9. doi: 10.1016/j.toxicon.2007.09.008. Epub 2007 Sep 29.
Ref 7 The tarantula toxins ProTx-II and huwentoxin-IV differentially interact with human Nav1.7 voltage sensors to inhibit channel activation and inactivation. Mol Pharmacol. 2010 Dec;78(6):1124-34. doi: 10.1124/mol.110.066332. Epub 2010 Sep 20.
Ref 8 Common molecular determinants of tarantula huwentoxin-IV inhibition of Na+ channel voltage sensors in domains II and IV. J Biol Chem. 2011 Aug 5;286(31):27301-10. doi: 10.1074/jbc.M111.246876. Epub 2011 Jun 9.
Ref 9 Potency optimization of Huwentoxin-IV on hNav1.7: a neurotoxin TTX-S sodium-channel antagonist from the venom of the Chinese bird-eating spider Selenocosmia huwena. Peptides. 2013 Jun;44:40-6. doi: 10.1016/j.peptides.2013.03.011. Epub 2013 Mar 19.
Ref 10 Engineering potent and selective analogues of GpTx-1, a tarantula venom peptide antagonist of the Na(V)1.7 sodium channel. J Med Chem. 2015 Mar 12;58(5):2299-314. doi: 10.1021/jm501765v. Epub 2015 Feb 19.
Ref 11 Gating modifier toxins isolated from spider venom: Modulation of voltage-gated sodium channels and the role of lipid membranes. J Biol Chem. 2018 Jun 8;293(23):9041-9052. doi: 10.1074/jbc.RA118.002553. Epub 2018 Apr 27.
Ref 12 Screening, large-scale production and structure-based classification of cystine-dense peptides. Nat Struct Mol Biol. 2018 Mar;25(3):270-278. doi: 10.1038/s41594-018-0033-9. Epub 2018 Feb 26.
Ref 13 Chemical Synthesis, Proper Folding, Na(v) Channel Selectivity Profile and Analgesic Properties of the Spider Peptide Phlotoxin 1. Toxins (Basel). 2019 Jun 21;11(6):367. doi: 10.3390/toxins11060367.
Ref 14 Analysis of the structural and molecular basis of voltage-sensitive sodium channel inhibition by the spider toxin huwentoxin-IV (-TRTX-Hh2a). J Biol Chem. 2013 Aug 2;288(31):22707-20. doi: 10.1074/jbc.M113.461392. Epub 2013 Jun 12.
Ref 15 Spider peptide toxin HwTx-IV engineered to bind to lipid membranes has an increased inhibitory potency at human voltage-gated sodium channel hNa(V)1.7. Biochim Biophys Acta Biomembr. 2017 May;1859(5):835-844. doi: 10.1016/j.bbamem.2017.01.020. Epub 2017 Jan 20.
Ref 16 The structure, dynamics and selectivity profile of a NaV1.7 potency-optimised huwentoxin-IV variant. PLoS One. 2017 Mar 16;12(3):e0173551. doi: 10.1371/journal.pone.0173551. eCollection 2017.
Ref 17 Structures of human Na(v)1.7 channel in complex with auxiliary subunits and animal toxins. Science. 2019 Mar 22;363(6433):1303-1308. doi: 10.1126/science.aaw2493. Epub 2019 Feb 14.
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