CharyBDotoxin(ChTx) isa37aminoacidpeptideisolatedfromthevenomofthe scorpionLeiurusquinquestriatushebraeus thatblocks voltage-gatedandlargeconductanceCa2+ activatedK+ channels KCa1.1 innanomolarconcentrations(IC50~3nM).ThisblockadecauseshyperexcitABIlityofthenervoussystem.ThetoxinreversIBLyblockschannelactivitybyinteractingattheexternalporeofthechannelproteinwithanapparentKdof2.1nM.ChTXalsoblocksKCa3.1 (IC50 5nM), Kv1.2 (IC50 14nM), Kv1.3 (IC50 2.6nM)and Kv1.6 (IC50 2nM)channels.
Productcode:N/A.Categories:KCachannels,Kvchannels,Potassiumchannels.Tags:95751-30-7,kv,SK.
AAsequence:Pyr-Phe-Thr-Asn-Val-Ser-Cys7-Thr-Thr-Ser-Lys-Glu-Cys13-Trp-Ser-Val-Cys17-Gln-Arg-Leu-His-Asn-Thr-Ser-Arg-Gly-Lys-Cys28-Met-Asn-Lys-Lys-Cys33-Arg-Cys35-Tyr-Ser-OH
(DisulfidebondsbetweenCys7-Cys28,Cys13-Cys33,andCys17-Cys35)
Length(aa): 37
Formula: C176H277N57O55S7
MolecularWeight: 4295.90Da
Appearance: Whitelyophilizedsolid
Solubility: waterandsalinebuffer
CASnumber: 95751-30-7
Source: Synthetic
Purityrate: >97%
Charybdotoxin(ChTX),aproteinpresentinthevenomofthescorpionLeiurusquinquestriatusvar.hebraeus,hasbeenpurifiedtohomogeneitybyacombinationofion-exchangeandreversed-phasechromatography.Polyacrylamidegelelectrophoresis,aminoacidanalysis,andcompleteaminoacidsequencedeterminationofthepureproteinrevealthatitconsistsofasinglepolypeptidechainof4.3kDa.PurifiedChTXisapotentandselectiveinhibitoroftheapproximately220-pSCa2+-activatedK+channelpresentinGH3anteriorpituitarycellsandprimarybovineaorticsmoothmusclecells.ThetoxinreversiblyblockschannelactivitybyinteractingattheexternalporeofthechannelproteinwithanapparentKdof2.1nM.TheprimarystructureofChTXissimilartoanumberofneurotoxinsofdiverseorigin,whichsuggeststhatChTXisamemberofasuperfamilyofproteinsthatmodifyion-channelactivities.Onthebasisofthissimilarity,thethree-dimensionalstructureofChTXhasbeenmodeledfromtheknowncrystalstructureofalpha-bungarotoxin.ThesestudiesindicatethatChTXisusefulasaprobeofCa2+-activatedK+-channelfunctionandsuggestthattheproposedtertiarystructureofChTXmayprovideinsightintothemechanismofchannelblock.
Gimenez-GallegoG.,etal.(1988)Purification,sequence,andmodelstructureofcharybdotoxin,apotentselectiveinhibitorofcalcium-activatedpotassiumchannels.Proc.Natl.Acad.Sci.U.S.A.PMID:2453055
Mechanismofcharybdotoxinblockofavoltage-gatedK+channel.
CharybdotoxinblockofaShakerK+channelwasstudiedinXenopusoocytemacropatches.Toxinonrateincreaseslinearlywithtoxinconcentrationinanionicstrength-dependentfashionandiscompetitivelydiminishedbytetraethylammonium.OnrateisinsensitivetotransmembranevoltageandtoK+ontheoppositesideofthemembrane.Conversely,toxinoffrateisinsensitivetotoxinconcentration,ionicstrength,andaddedtetraethylammoniumbutisenhancedbymembranedepolarizationorK+(orNa+)inthetranssolution.ChargeneutralizationofcharybdotoxinLys27,however,rendersoffratevoltageinsensitive.Ourresultsarguethatblockofvoltage-gatedK+channelsresultsfromthebindingofonetoxinmolecule,sothatLys27enterstheporeandinteractswithK+(orNa+)intheionconductionpathway.
GoldsteinSA,MillerC.(1993)Mechanismofcharybdotoxinblockofavoltage-gatedK+channel.BiophysJ.PMID:7506068
ThecharybdotoxinreceptorofaShakerK+channel:peptideandchannelresiduesmediatingmolecularrecognition.
Charybdotoxin(CTX)isapeptideofknownstructurethatinhibitsShakerK+channelsbyapore-blockingmechanism.Pointmutagenesisofall30solvent-exposedresiduesidentifiedthepartoftheCTXmolecularsurfacemakingcontactwiththereceptorintheK+channel.Allclose-contactresiduesareclusteredinawell-definedinteractionsurface;theshapeofthissurfaceimpliesthattheouteropeningoftheShakerchannelconductionporeabruptlywidenstoa25x35Aplateau.AmutagenicscanoftheS5-S6linkersequenceoftheShakerK+channelidentifiedthosechannelresiduesinfluencingCTXbindingaffinity.TheShakerresiduesmakingthestrongestcontributiontotoxinbindingarelocatedclosetothepore-liningsequence,andmoredistantresiduesonbothsidesofthisregioninfluenceCTXbindingweakly,probablybyanelectrostaticmechanism.ComplementarymutagenesisofbothCTXandShakersuggeststhatShaker-F425contactsaspecificareanearT8andT9ontheCTXmolecularsurface.ThiscontactpointconstrainsShaker-F425tobelocatedata20Ar
ADIaldistancefromtheporeaxisand10-15Aabovethe“floor”oftheCTXreceptor.
GoldsteinSA,etal.(1994)ThecharybdotoxinreceptorofaShakerK+channel:peptideandchannelresiduesmediatingmolecularrecognition.Neuron.PMID:7516689
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Smartox Biotechnology 是全球唯一一家专门生产动物毒液多肽毒素，用于细胞离子通道功能研究的生物医药公司。多肽毒素在生物制药领域具有重要的使用价值。Smartox Biotechnology 于 2009 年由来自 Grenoble 神经科学研究所 (Grenoble Institute of Neuroscience) 的 Michel de waard 博士创立, Smartox Biotechnology 专门研究动物毒液，制作合成多种毒液中的多肽成分（常称为毒素）。 De Waard 博士研究离子通道与毒素多肽的关系，尤其是鉴定、开发毒素多肽作为治疗性分子或细胞穿透肽 (cell penetrating peptides, CPP) 。其研究团队在毒液分离，药理性活性肽鉴定、富半胱氨酸肽定性、制作和优化等方面具有独特、丰富的经验。 2010 年， Smartox Biotechnolgy 被法国研究部 (Ministry of Research) 授予“新兴企业 OSEO 奖 (OSEO prize for emerging businesses) ”。
