ω-conotoxin-GVIA(omegaconotoxinGVIA)isaconotoxinthathhasbeenisolatedfromthevenomoftheconeConusgeographus. ω-conotoxinGVIA actsatpresynapticmembranes.Itbindsandblocksspecifically voltage-dependentN-typeCa2+channels Cav2.2channel withanED50 of68pM.
Description:
AAsequence: H-Cys1-Lys-Ser-Hyp-Gly-Ser-Ser-Cys8-Ser-Hyp-Thr-Ser-Tyr-Asn-Cys15-Cys16-Arg-Ser-Cys19-Asn-Hyp-Tyr-Thr-Lys-Arg-Cys26-Tyr-NH2
Hyp:hydroxyproline
(DisulfidebondsbetweenCys1-Cys16,Cys8-Cys19 andCys15-Cys26)
Length(aa): 27
Formula: C120H182N38O43S6
MolecularWeight: 3036.05Da
Appearance: Whitelyophilizedsolid
Solubility: waterandsalinebuffer
CASnumber: [106375-28-4]Source: Synthetic
Purityrate: >95%
Reference:
Structure-functionrelationshipsofomega-conotoxinGVIA.Synthesis,structure,calciumchannelbinding,andfunctionalassayofalanine-substitutedanalogues
Thestructure-functionrelationshipsoftheN-typecalciumchannelblocker,omega-conotoxinGVIA(GVIA),havebeenelucidatedbystructural,binding&invitro&invivofunctionalstudiesofalanine-substitutedanaloguesofthenativemolecule.Alaninewassubstitutedatallnon-bridgingpositionsinthesequence.Inmostcasesthestructureoftheanaloguesinaqueoussolutionwasshowntobenative-likeby1HNMRspectroscopy.Minorconformationalchangesobservedinsomecaseswerecharacterizedbytwo-dimensionalNMR.ReplacementofLys2&Tyr13withAlacausedreductionsinpotencyofmorethan2ordersofmagnitudeinthreefunctionalassays(sympatheticnervestimulationofratisolatedvasdeferens,rightatrium&mesentericartery)&aratbrainmembranebindingassay.ReplacementofseveralotherresidueswithAla(particularlyArg17,Tyr22&Lys24)resultedinsignificantreductionsinpotency(<100-fold)inthefunctionalassays,butnotthebindingassay.Thepotenciesoftheanalogueswerestronglycorrelatedbetweenthedifferentfunctionalassaysbutnotbetweenthefunctionalassays&thebindingassay.Thus,thephysiologicallyrelevantassaysemployedinthisstudyhaveshownthatthehighaffinityofGVIAfortheN-typecalciumchannelistheresultofinteractionsbetweenthechannelbindingsite&thetoxinatmoresitesthanthepreviouslyidentifiedLys2&Tyr13.
