Vc1.1 (P00004) Protein Card

General Information
Name Vc1.1
Alternative name(s) ACV1
Organism synthetic construct
Protein Type Synthetic
Parent VcIA
Notes Inhibition of N-type Ca2+ channel current through the GABAB in rat DRG neurons with an IC50 of 1.7nM (Callaghan et al. 2008) and 24.6nM in mouse DRG of an a9 KO mouse (Callaghan et al. 2010). The specific receptor remains unclear.

Classification
Conopeptide class conotoxin
Gene superfamily
Cysteine framework I
Pharmacological family alpha conotoxin

Sequence
GCCSDPRCNYDHPEIC(nh2)
Modified residues
positionsymbolname
17nh2C-term amidation
Average Mass 1806.97
Monoisotopic Mass 1805.64
Isoelectric Point 5.63
Extinction Coefficient [280nm] 1490.00

Activity

IC50: Nicotinic acetylcholine receptors

TargetOrganismIC50nhillAgonistRef
α1β1γδR. norvegicus>30uMAchClark,R.J. et al. (2006)
α3α5β2R. norvegicus7.2uM+/-0.21.3AchClark,R.J. et al. (2006)
α3α5β4R. norvegicus>30uMAchClark,R.J. et al. (2006)
α3β2R. norvegicus7.3uM+/-0.71.7AchClark,R.J. et al. (2006)
>1uM30-100mM AchSafavi-Hemami,H. et al. (2011)
5.5uM10uM AchHalai,R. et al. (2009)
α3β4R. norvegicus>3uM10uM AchHalai,R. et al. (2009)
4.2uM+/-1.61.3AchClark,R.J. et al. (2006)
α4β2R. norvegicus>30uMAchClark,R.J. et al. (2006)
α4β4R. norvegicus>30uMAchClark,R.J. et al. (2006)
α6/α3β2β3R. norvegicus140nM100uM AchVincler,M. et al. (2006)
α6/α3β4R. norvegicus980nM100uM AchVincler,M. et al. (2006)
α7R. norvegicus7.1uM10uM AchHalai,R. et al. (2009)
>1uM30-100mM AchSafavi-Hemami,H. et al. (2011)
>30uMAchClark,R.J. et al. (2006)
α9α10H. sapiens(human a9 rat a10)975.4nM+/-3140.850uM AchYu,R. et al. (2013)
(human a9 rat a10)549nM10uM AchHalai,R. et al. (2009)
R. norvegicus70.0nM+/-251.550uM AchYu,R. et al. (2013)
19nM10uM AchVincler,M. et al. (2006)
64.2nM+/-151.130uM AchNevin,S.T. et al. (2007)
109nM30-100 mM AchSafavi-Hemami,H. et al. (2011)
109nM10uM AchHalai,R. et al. (2009)

Percentage inhibition: Nicotinic acetylcholine receptors

TargetOrganism% inhibitionConcentrationAgonistRef
α9α10Unknown65+/-5100nM30uM Ach 16 Klimis,H. et al. (2011)
89+/-51uM30uM AchKlimis,H. et al. (2011)

Synthetic variants
Cyclic Vc1.1GGAAGGCIEPHDYNCRPDSCCG
Cyclic Vc1.1[D11E,E14A]GGAAGGCIAPHEYNCRPDSCCG
Vc1.1 [Cys2Agl,Cys8Agl](nh2)CIEPHDYN(Agl)RPDSC(Agl)G
Vc1.1 [Cys3Agl,Cys16Agl](nh2)(Agl)IEPHDYNCRPDS(Agl)CG
Vc1.1 [E14Gla](nh2)CI(Gla)PHDYNCRPDSCCG
Vc1.1 [P6O](nh2)CIEPHDYNCRODSCCG
Vc1.1[D11A](nh2)CIEPHAYNCRPDSCCG
Vc1.1[D11K](nh2)CIEPHKYNCRPDSCCG
Vc1.1[D5A](nh2)CIEPHDYNCRPASCCG
Vc1.1[D5K](nh2)CIEPHDYNCRPKSCCG
Vc1.1[E14A](nh2)CIAPHDYNCRPDSCCG
Vc1.1[E14D](nh2)CIDPHDYNCRPDSCCG
Vc1.1[E14K](nh2)CIKPHDYNCRPDSCCG
Vc1.1[G1A](nh2)CIEPHDYNCRPDSCCA
Vc1.1[G1D](nh2)CIEPHDYNCRPDSCCD
Vc1.1[G1K](nh2)CIEPHDYNCRPDSCCK
Vc1.1[H12A](nh2)CIEPADYNCRPDSCCG
Vc1.1[H12D](nh2)CIEPDDYNCRPDSCCG
Vc1.1[H12K](nh2)CIEPKDYNCRPDSCCG
Vc1.1[I15A](nh2)CAEPHDYNCRPDSCCG
Vc1.1[I15D](nh2)CDEPHDYNCRPDSCCG
Vc1.1[I15K](nh2)CKEPHDYNCRPDSCCG
Vc1.1[N9A](nh2)CIEPHDYACRPDSCCG
Vc1.1[N9D](nh2)CIEPHDYDCRPDSCCG
Vc1.1[N9F](nh2)CIEPHDYFCRPDSCCG
Vc1.1[N9G](nh2)CIEPHDYGCRPDSCCG
Vc1.1[N9I](nh2)CIEPHDYICRPDSCCG
Vc1.1[N9K](nh2)CIEPHDYKCRPDSCCG
Vc1.1[N9L](nh2)CIEPHDYLCRPDSCCG
Vc1.1[N9W](nh2)CIEPHDYWCRPDSCCG
Vc1.1[P13A](nh2)CIEAHDYNCRPDSCCG
Vc1.1[P13D](nh2)CIEDHDYNCRPDSCCG
Vc1.1[P13K](nh2)CIEKHDYNCRPDSCCG
Vc1.1[P6A](nh2)CIEPHDYNCRADSCCG
Vc1.1[P6D](nh2)CIEPHDYNCRDDSCCG
Vc1.1[P6K](nh2)CIEPHDYNCRKDSCCG
Vc1.1[R7A](nh2)CIEPHDYNCAPDSCCG
Vc1.1[R7D](nh2)CIEPHDYNCDPDSCCG
Vc1.1[R7K](nh2)CIEPHDYNCKPDSCCG
Vc1.1[S4A](nh2)CIEPHDYNCRPDACCG
Vc1.1[S4D](nh2)CIEPHDYNCRPDDCCG
Vc1.1[S4K,N9A](nh2)CIEPHDYACRPDKCCG
Vc1.1[S4K](nh2)CIEPHDYNCRPDKCCG
Vc1.1[S4R](nh2)CIEPHDYNCRPDRCCG
Vc1.1[Y10A](nh2)CIEPHDANCRPDSCCG
Vc1.1[Y10D](nh2)CIEPHDDNCRPDSCCG
Vc1.1[Y10K](nh2)CIEPHDKNCRPDSCCG
[G]Vc1.1[GLPETGGS]SGGTEPLGCIEPHDYNCRPDSCCGG
[Ser3]Vc1.1(1-8)(nh2)CRPDSSCG
cVc1.1-L1KGKXKGCIEPHDYNCRPDSCCG
cVc1.1-L2VGXGXGCIEPHDYNCRPDSCCG
cVc1.1-L3EXEXEGCIEPHDYNCRPDSCCG
hVc1.1GGAAGGCIEPHDYNFRPDSCHG

References
Clark,R.J., Fischer,H., Nevin,S.T., Adams,D.J. and Craik,D.J. (2006) The synthesis, structural characterization, and receptor specificity of the alpha-conotoxin Vc1.1 J. Biol. Chem. 281:23254-23263
Sandall,D.W., Satkunanathan,N., Keays,D.A., Polidano,M.A., Liping,X., Pham,V., Down,J.G., Khalil,Z., Livett,B.G. and Gayler,K.R. (2003) A novel alpha-conotoxin identified by gene sequencing is active in suppressing the vascular response to selective stimulation of sensory nerves in vivo Biochemistry 42:6904-6911
Safavi-Hemami,H., Siero,W.A., Kuang,Z., Williamson,N.A., Karas,J.A., Page,L.R., MacMillan,D., Callaghan,B., Kompella,S.N., Adams,D.J., Norton,R.S., and Purcell,A.W. (2011) Embryonic toxin expression in the cone snail Conus victoriae: primed to kill or divergent function? J. Biol. Chem. 286:22546-22557
Halai,R., Clark,R.J., Nevin,S.T., Jensen,J.E., Adams,D.J. and Craik,D.J. (2009) Scanning mutagenesis of alpha-conotoxin Vc1.1 reveals residues crucial for activity at the alpha9alpha10 nicotinic acetylcholine receptor. J. Biol. Chem.
Vincler,M., Wittenauer,S., Parker,R., Ellison,M., Olivera,B.M. and McIntosh,J.M. (2006) Molecular mechanism for analgesia involving specific antagonism of alpha9alpha10 nicotinic acetylcholine receptors. Proc. Natl. Acad. Sci. U.S.A. 103:17880-17884
Cuny,H., Kompella,S.N., Tae,H.S., Yu,R. and Adams,D.J. (2016) Key Structural Determinants in the Agonist Binding Loops of Human β2 and β4 Nicotinic Acetylcholine Receptor Subunits Contribute to α3β4 Subtype Selectivity of α-Conotoxins. J. Biol. Chem. 291:23779-23792
Klimis,H., Adams,D.J., Callaghan,B., Nevin,S., Alewood,P.F., Vaughan,C.W., Mozar,C.A. and Christie,M.J. (2011) A novel mechanism of inhibition of high-voltage activated calcium channels by α-conotoxins contributes to relief of nerve injury-induced neuropathic pain. Pain 152:259-266
Nevin,S.T., Clark,R.J., Klimis,H., Christie,M.J., Craik,D.J. and Adams,D.J. (2007) Are alpha9alpha10 nicotinic acetylcholine receptors a pain target for alpha-conotoxins? Mol. Pharmacol. 72:1406-1410
Callaghan,B., Haythornthwaite,A., Berecki,G., Clark,R.J., Craik,D.J. and Adams,D.J. (2008) Analgesic alpha-conotoxins Vc1.1 and Rg1A inhibit N-type calcium channels in rat sensory neurons via GABAB receptor activation. J. Neurosci. 28:10943-10951
Yu,R., Kompella,S.N., Adams,D.J., Craik,D.J. and Kaas,Q. (2013) Determination of the α-Conotoxin Vc1.1 Binding Site on the α9α10 Nicotinic Acetylcholine Receptor. J. Med. Chem.

Internal links
Nucleic acids
Structure SOLUTION STRUCTURE OF ALPHA-CONOTOXIN VC1.1

External links
Ncbi 2H8S_A

Tools