GVIA (P01546) Protein Card

General Information
Name GVIA
Alternative name(s) G6a,SNX-124,Shaker peptide
Organism Conus geographus (Geography cone)
Organism region Indo-Pacific
Organism diet piscivorous
Protein Type Wild type
Protein precursor GVIA precursor (820)
GVIA precursor (5749)
Notes Calcium Channel Blocker; Paralysis in lower vertebrates; shaking symptoms upon ic injection in mice. Kim et al. have performed an ala scan of GVIA (see references). GVIA was also shown by Horne et al. 1991,to bind to the α1 subunit of Torpedo nAChR.

Classification
Conopeptide class conotoxin
Gene superfamily O1 superfamily
Cysteine framework VI/VII
Pharmacological family omega conotoxin

Sequence
CKSOGSSCSOTSYNCCRSCNOYTKRCY(nh2)
Modified residues
positionsymbolname
4O4-Hydroxyproline
10O4-Hydroxyproline
21O4-Hydroxyproline
28nh2C-term amidation
Sequence evidence protein level
Average Mass 3037.34
Monoisotopic Mass 3035.15
Isoelectric Point 12.58
Extinction Coefficient [280nm] 4470.00

Activity

IC50: Voltage-Gated Calcium Channels

TargetOrganismIC50CompetitorRef
Cav2.1R. norvegicus1.05uMMVIIALewis,R.J. et al. (2000)
Cav2.2R. norvegicus38pMGVIALewis,R.J. et al. (2000)
2.02pM1nM CnVIIAFavreau,P. et al. (2001)
3.7-4.3pM1nM GVIAFavreau,P. et al. (2001)
28pMGVIAMould,J. et al. (2004)
134pMMVIIAMiljanich,G.P. et al. (1993)

Synthetic variants
GVIA [O10>K]CKSOGSSCSKTSYNCCRSCNOYTKRCY(nh2)
GVIA[C8U,C19U]CKSOGSSUSOTSYNCCRSUNOYTKRCY(nh2)

References
Olivera,B.M., McIntosh,J.M., Cruz,L.J., Luque,F.A. and Gray,W.R. (1984) Purification and sequence of a presynaptic peptide toxin from Conus geographus venom Biochemistry 23:5087-5090
Sato,K., Park,N.G., Kohno,T., Maeda,T., Kim,J.I., Kato,R. and Takahashi,M. (1993) Role of basic residues for the binding of omega-conotoxin GVIA to N-type calcium channels Biochem. Biophys. Res. Commun. 194:1292-1296
Kim,J.I., Takahashi,M., Ogura,A., Kohno,T., Kudo,Y. and Sato,K. (1994) Hydroxyl group of Tyr13 is essential for the activity of omega-conotoxin GVIA, a peptide toxin for N-type calcium channel J. Biol. Chem. 269:23876-23878
Lew,M.J., Flinn,J.P., Pallaghy,P.K., Murphy,R., Whorlow,S.L., Wright,C.E., Norton,R.S. and Angus,J.A. (1997) Structure-function relationships of omega-conotoxin GVIA. Synthesis, structure, calcium channel binding, and functional assay of alanine-substituted analogues J. Biol. Chem. 272:12014-12023
Davis,J.H., Bradley,E.K., Miljanich,G.P., Nadasdi,L., Ramachandran,J. and Basus,V.J. (1993) Solution structure of omega-conotoxin GVIA using 2-D NMR spectroscopy and relaxation matrix analysis Biochemistry 32:7396-7405
Pallaghy,P.K. and Norton,R.S. (1999) Refined solution structure of omega-conotoxin GVIA: implications for calcium channel binding J. Pept. Res. 53:343-351
Rivier,J., Galyean,R., Gray,W.R., Azimi-Zonooz,A., McIntosh,J.M., Cruz,L.J. and Olivera,B.M. (1987) Neuronal calcium channel inhibitors. Synthesis of omega-conotoxin GVIA and effects on 45Ca uptake by synaptosomes J. Biol. Chem. 262:1194-1198
Mould,J., Yasuda,T., Schroeder,C.I., Beedle,A.M., Doering,C.J., Zamponi,G.W., Adams,D.J. and Lewis,R.J. (2004) The alpha2delta auxiliary subunit reduces affinity of omega-conotoxins for recombinant N-type (Cav2.2) calcium channels J. Biol. Chem. 279:34705-34714
Kerr,L.M. and Yoshikami,D. (1984) A venom peptide with a novel presynaptic blocking action. Nature 308:282-284
Yoshikami,D. and Olivera,B.M. (1989) The inhibitory effects of omega-conotoxins on Ca channels and synapses. Ann. N. Y. Acad. Sci. 560:230-248
Lampe,R.A., Lo,M.M., Keith,R.A., Horn,M.B., McLane,M.W. and Spreen,R.C. (1993) Effects of site-specific acetylation on omega-conotoxin GVIA binding and function. Biochemistry 32:3255-3260
Flinn,J.P., Pallaghy,P.K., Lew,M.J., Murphy,R. and Norton,R.S. (1999) Role of disulfide bridges in the folding, structure and biological activity of omega-conotoxin GVIA. Biochim. Biophys. Acta 1434:177-190
Horne,W.A., Hawrot,E. and Tsien,R.W. (1991) omega-Conotoxin GVIA receptors of Discopyge electric organ. Characterization of omega-conotoxin binding to the nicotinic acetylcholine receptor. J. Biol. Chem. 266:13719-13725

Internal links
Protein Precursor GVIA precursor (820)
GVIA precursor (5749)
Nucleic acids
Structure SOLUTION STRUCTURE OF OMEGA-CONOTOXIN GVIA USING 2-D NMR SPECTROSCOPY AND RELAXATION MATRIX ANALYSIS
OMEGA-CONOTOXIN GVIA, A N-TYPE CALCIUM CHANNEL BLOCKER
STRUCTURE OF THE CALCIUM CHANNEL BLOCKER OMEGA CONOTOXIN GVIA, NMR, 20 STRUCTURES

External links
Ncbi 2CCO_A, 1TTL_A, 1OMC_A

Tools