Maurotoxin isacomponentofthevenomofScorpiomauruspalmatus. Maurotoxin isamemberoftheα-KTx6.2scorpiontoxinfamily.Itblocksvoltage-gatedpotassiumchannels(KV1.1/KCNA1,KV1.2/KCNA2,andKV1.3/KCNA3)andinhibitsapamin-sensitivesmallconductancecalcium-activatedchannels(SKchannels),particularlyKCa3.1(IKca1,SK4).TheblockageofKv1.2occurswithhighaffinity.
Productcode:N/A.Categories:Kvchannels,Potassiumchannels.Tags:kv,SK.
AAsequence: Val-Ser-Cys3-Thr-Gly-Ser-Lys-Asp-Cys9-Tyr-Ala-Pro-Cys13-Arg-Lys-Gln-Thr-Gly-Cys19-Pro-Asn-Ala-Lys-Cys24-Ile-Asn-Lys-Ser-Cys29-Lys-Cys31-Tyr-Gly-Cys34-NH2
Disulfidebonds: Cys3-Cys24,Cys9-Cys29,Cys13-Cys19 andCys31 -Cys34
Length(aa): 34
Formula: C145H231N45O47S8
MolecularWeight: 3612.55Da
Appearance:Whitelyophilizedsolid
Solubility: waterorsalinebuffer
CASnumber: notavailable
Source: Synthetic
Purityrate: >95%
Maurotoxin(MTX)isa34-residuetoxinthatwasisolatedinitiallyfromthevenomofthescorpionScorpiomauruspalmatus.Unliketheothertoxinsoftheα-KTx6family(Pi1,Pi4,Pi7,andHsTx1),MTXexhibitsauniquedisulfidebridgeorganizationofthetypeC(1)C(5),C(2)C(6),C(3)C(4),andC(7)C(8)(insteadoftheconventionalC(1)C(5),C(2)C(6),C(3)C(7),andC(4)C(8),hereinreferredtoasPi1-like)thatdoesnotpreventitsfoldingalongtheclassicα/βscaffoldofscorpiontoxins.MTX(Pi1)isanMTXvariantwithaconventionalpatternofdisulfidebridgingwithoutanyprimarystructurealterationofthetoxin.Here,usingMTXand/orMTX(Pi1)asmodels,weinvestigatedhowthetypeoffoldinginfluencestoxinrecognitionoftheShakerBpotassiumchannel.AminoacidresiduesofMTXthatwerestudiedforShakerBrecognitionwereselectedonthebasisoftheirhomologouspositioninchary
BDotoxin,athreedisulfide-bridgedscorpiontoxinalsoactiveonthischanneltype.TheseresiduesfavoredeitheranMTX-orMTX(Pi1)-likefolding.OurdataindicateclearlythatLys(23)andTyr(32)(twooutoftenaminoacidresiduesstudied)arethemostimportantresiduesforShakerBchannelblockagebyMTX.ForactivityonSKCachannels,thesameaminoacidresiduesalsoaffect,directlyorindirectly,therecognitionofSKchannels.ThemolecularmodelingtechniqueandcomputeddockingindicatetheexistenceofacorrelationbetweenthehalfcystinepairingsofthemutatedanalogsandtheiractivityontheShakerBK(+)channel.Overall,mutationsinMTXcould,orcouldnot,changethereorganizationofdisulfidebridgesofthismoleculewithoutaffectingitsα/βscaffold.However,changingofthepeptidebackbone(crosslinkingdisulfidebridgesfromMTX-liketypevsMTX(Pi1)-liketype)appearstohavelessimpactonthemoleculeactivitythanmutationofcertainkeyaminoacidssuchasLys(23)andTyr(32)inthistoxin.FajlounZ,
etal.,(2011)Analysisoftheinteractingsurfaceofmaurotoxinwiththevoltage-gatedShakerBK(+)channel.
JPeptSci. PMID: 21308876Maurotoxinisa34-residuetoxinisolatedfromthevenomoftheTunisianchactoidscorpionScorpiomauruspalmatusandcontainsfourdisulfidebridgesthatarenormallyfoundinlong-chaintoxinsof60-70aminoacidresidues,whichaffectvoltage-gatedsodiumchannels.However,despitetheunconventionaldisulfide-bridgepatternofmaurotoxin,theconformationofthistoxinremainssimilartothatofothertoxinsactingonpotassiumchannels.Here,weanalyzedtheeffectsofsyntheticmaurotoxinonvoltage-gatedShakerpotassiumchannels(ShB)expressedinXenopusoocytes.Maurotoxinproducesastrong,butrevers
IBLe,inhibitionoftheShBK+currentwithanIC50of2nM.Increasingconcentrationsofthetoxininduceaprogressivelyhigherblockatsaturatingconcentrations.Atnonsaturatingconcentrationsofthetoxin(5-20nM),thechannelblockappearsslightlymorepronouncedatthresholdpotentialssuggestingthatthetoxinmayhaveahigheraffinityfortheclosedstateofthechannel.Atthesinglechannellevel,thetoxindoesnotmodifytheunitarycurrentamplitude,butdecreasesensemblecurrentsbyincreasingthenumberofdepolarizingepochsthatfailedtoelicitanyopening.ApointmutationofLys23toalanineinmaurotoxinproducesa1000-foldreductionintheIC50ofblockbythetoxinsuggestingtheimportanceofthischargedresiduefortheinteractionwiththechannel.MaurotoxindoesnotaffectK+currentscarriedbyKir2.3channelsinoocytesorNa+currentscarriedbythealphaIIachannelexpressedinCHOcells.Carlier,E.
,etal.(2000)Effectofmaurotoxin,afourdisulfide-bridgedtoxinfromthechactoidscorpionScorpiomaurus,onShakerK+channels,
JPept. PMID: 10888198
Maurotoxin,a toxin fromthevenomoftheTunisianchactoid scorpion Scorpiomaurus,hasbeenpurifiedtohomogeneitybygelfiltration/reversed-phaseHPLC,andcharacterized.ItisabasicandC-terminalamidated34-residuepolypeptidecross-linkedby four disulfide bridges.FromEdmansequencingresults,onlysixdifferentpairingsbetweenthefirstsixhalf-cystineswereretainedwhereasa disulfide bridgewaspredictedbetweenthetwohalf-cystinesinpositions31and34.Modellingbasedonthestructureofcharybdotoxinfavoredtwodifferentpairings,oneofwhichpossessedtwodisulfidesincommonwiththegeneralmotifof scorpion toxins.Thesolid-phasetechniquewasusedtoobtainsynthetic maurotoxin,sMTX.Thehalf-cystinepairingsofsMTXweredeterminedbyenzymaticcleavageandwerefoundtobeCys3Cys24,Cys9-Cys29,Cys13-Cys19,andCys31-34,inagreementwithexperimentaldataobtainedwithnatural maurotoxin.Bothnaturalandsyntheticmaurotoxinswerelethaltomicefollowingintracerebroventricularinjection(LD50,80ng/mouse).TheyblockedtheKv1.1,Kv1.2,andKv1.3 channels expressedinXenopusoocyteswithalmostidenticalhalf-effects(IC50)intherangeof40,0.8and150nM,respectively.Theyalsocompetedwith125I-apamin(SKcachannelblocker)and125I-kaliotoxin(Kvchannelblocker)forbindingtoratbrainsynaptosomeswithIC50ofabout5and0.03nM.Asthenaturalandsyntheticmaurotoxinsexhibitindistinguishablephysicochemicalandpharmacologicalproperties,theyarelikelytoadoptthesamehalf-cystinepairingpatternwhichisuniqueamongknown scorpion toxins.However,this disulfide organizationisdifferentfromthosereportedforPandinusimperatorandHeterometrusspinnifertoxins1(Pi1andHsTx1),twonovel four-disulfide bridged K+channel-acting scorpion toxin sharingabout50-70%sequenceidentitywith maurotoxin.
Rochat,H., etal.(1998)Maurotoxin,afourdisulfidebridgesscorpiontoxinactingonK+channels, Toxicon.PMID: 9792177
Solutionstructureofmaurotoxin,ascorpiontoxinfromScorpiomaurus,withhighaffinityforvoltage-gatedpotassiumchannels
Maurotoxin (MTX),purifiedfromthescorpionid Scorpio maurus isapotentligandfor potassium channels.ItshowsabroadspecificityasbeingactiveonKv1.1(Kd=37nM),Kv1.2(Kd=0.8nM),Kv1.3(Kd=150nM) voltage-gated potassium channels,aswellasonsmall-conductancecalcium-activated potassium channels.Ithasauniquedisulfidepairingamongthe scorpion toxinsfamily.The solution structure ofMTXhasbeendeterminedby2D-NMRtechniques,whichledtothefulldescriptionofits3Dconformation:abendedhelixfromresidues6to16connectedbyalooptoatwo-strandedantiparallelbetasheet(residues23to26and28to31).TheinteractionofMTXwiththeporeregionoftheKv1.2 potassium channelhasbeenmodeledaccordingtotheirchargeanisotropy.The structure ofMTXissimilartoothershort scorpion toxinsdespiteitspeculiardisulfidepairing.ItsinteractionwiththeKv1.2channelinvolvesadipolemoment,whichguidesandorientsthe toxin ontothepore,towardthebindingsite,andwhichthusisresponsibleforthespecificity.
Blanc,E., etal.(1997)Solutionstructureofmaurotoxin,ascorpiontoxinfromScorpiomaurus,withhighaffinityforvoltage-gatedpotassiumchannels, Proteins. PMID: 9365987
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