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《A novel conotoxin framework with a helix-loop-helix (Cs alpha alpha) fold》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。
1、15986Biochemistry2005,44,15986-15996ANovelConotoxinFrameworkwithaHelix-Loop-Helix(CsR/R)Fold²CarolinaMoÈller,³,§SanazRahmankhah,³JanelleLauer-Fields,³JoseBubis,§GreggB.Fields,³andFrankMarõÂ*,³DepartmentofChemistryandBiochemistryandCenterofExcellenceinBiomedicalandMarineBiotechnology,FloridaAtla
2、nticUniVersity,BocaRaton,Florida33431,andDepartamentodeBiologõÂaCelular,UniVersidadSimoÂnBolõÂVar,Sartenejas1080,VenezuelaReceiVedJune10,2005;ReVisedManuscriptReceiVedSeptember26,2005ABSTRACT:Venomouspredatoryanimals,suchassnakes,spiders,scorpions,seaanemones,andconesnails,produceavarietyofhigh
3、lystablecystine-constrainedpeptidescaffoldsaspartoftheirneurochemicalstrategyforcapturingprey.Herewereportanewfamilyoffour-cystine,three-loopconotoxins(designatedframework14).Threepeptidesofthisfamily(flf14a-c)wereisolatedfromthevenomofConusfloridanusfloridensis,andone(vil14a)wasisolatedfromthe
4、venomofConusVillepinii,twoworm-huntingWesternAtlanticconesnailspecies.TheprimarystructureforthesepeptideswasdeterminedusingEdmandegradationsequencing,andtheircystinepairingwasassessedbylimitedhydrolysiswithacombinationofCNBrandchymotrypsinundernonreducing,nonalkylatingconditionsincombinationwit
5、hMALDI-TOFMSanalysisoftheresultingpeptidicfragments.CDspectraandnanoNMRspectroscopyoftheseconotoxinsdirectlyisolatedfromtheconesnailsrevealedahighlyhelicalsecondarystructureforthefourconotoxins.Sequence-specificnanoNMRanalysisatroomtemperaturerevealedawell-definedhelix-loop-helixtertiarystructu
6、rethatresemblesthatoftheCsR/Rscorpiontoxins-hefutoxin,-KTx1.3,andOm-toxins,whichadoptastablethree-dimensionalfoldwherethetwoR-helicesarelinkedbythetwodisulfidebridges.Oneoftheseconotoxins(vil14a)hasaLys/Tyrdyad,separatedbyapproximately6Å,whichisaconservedstructuralfeatureinK+channelblockers.T
7、hepresenceofthisframeworkinscorpionsandinconesnailsindicatesacommonmolecularimprintinthevenomofapparentlyunrelatedpredatoryanimalsandsuggestsacommonancestralgeneticorigin.Animalsthatutilizevenomtocaptureprey,suchassnakes,andachara
