Phrixotoxin-3 (PaurTx3orBeta-theraphotoxin-Ps1a)isavaluablepharmacologicaltooltostudyvoltage-gatedsodiumchannels.Phrixotoxin-3,originallyissuedfromthevenomofthetarantulaphrixotrichusauratus,hasbeenshowntoinhibitNav1.1,Nav1.2,Nav1.3,Nav1.4 and Nav1.5 withrespectiveIC50 valuesof610nM,0.6nM,42nM,288nMand72nM.ItisthusconsideredasoneofthemostpotentandalmostselectivemodulatorofNav1.2.
Productcode:N/A.Category:Sodiumchannels.Tag:nav1.2.
AAsequence: Asp-Cys2-Leu-Gly-Phe-Leu-Trp-Lys-Cys9-Asn-Pro-Ser-Asn-Asp-Lys-Cys16-Cys17-Arg-Pro-Asn-Leu-Val-Cys23-Ser-Arg-Lys-Asp-Lys-Trp-Cys30-Lys-Tyr-Gln-Ile-OH
Disulfidebridges: Cys2-Cys17,Cys9-Cys23,andCys16-Cys30
Length(aa): 34
Formula: C171H245N53O47S6
MolecularWeight: 4059.9Da
Appearance:Whitelyophilizedsolid
Solubility: waterorsalinebuffer
CASnumber: Notavailable
Source: Synthetic
Purityrate: >97%
Fournovelpeptidetoxinsthatactonvoltage-gatedsodiumchannelshavebeenisolatedfromtarantulavenoms:ceratotoxins1,2,and3(CcoTx1,CcoTx2,andCcoTx3)fromCeratogyruscornuatusandphrixotoxin3(PaurTx3)fromPhrixotrichusauratus.Thepharmacologicalprofilesofthesenewtoxinswerecharacterizedbyelectrophysiologicalmeasurementsonsixclonedvoltage-gatedsodiumchannelsubtypesexpressedinXenopuslaevisoocytes(Na(v)1.1/beta(1),Na(v)1.2/beta(1),Na(v)1.3/beta(1),Na(v)1.4/beta(1),Na(v)1.5/beta(1),andNa(v)1.8/beta(1)).Thesenoveltoxinsmodulatevoltage-gatedsodiumchannelswithpropertiessimilartothoseoftypicalgating-modifiertoxins,bothbycausingadepolarizingshiftingatingkineticsandbyblockingtheinwardcomponentofthesodiumcurrent.PaurTx3isoneofthemostpotentpeptidemodulatorsofvoltage-gatedsodiumchannelsdescribedthusfarfromspidervenom,modulatingNa(v)1.2withanIC(50)valueof0.6+/-0.1nM.CcoTx1andCcoTx2,differingbyonlyoneaminoacid,arepotentmodulatorsofdifferentvoltage-gatedsodiumchannelsubtypesfromthecentralnervoussystem,exceptforNa(v)1.3,whichisonlyaffectedbyCcoTx2.ThepotencyofCcoTx3islower,althoughthistoxinseemstobemoreselectiveforthetetrodotoxin-resistantchannelsubtypeNa(v)1.5/beta(1)(IC(50)=447+/-32nM).Inadditiontotheseresults,molecularmodelingindicatesthatsubtledifferencesintoxinsurfacesmayrelatetotheirdifferentpharmacologicalprofiles.Fur
Thermore,anevolutionarytraceanalysisofthesetoxinsandotherstructurallyrelatedthree-disulfidespidertoxinsprovidescluesfortheexplorationoftoxin-channelinteractionandfuturestructure-functionresearch.Bosmans,F.
etal (2006)FourNovelTarantulaToxinsasSelectiveModulatorsofVoltage-GatedSodiumChannelSubtypes.
MolecularPharmacology. PMID:16267209
