MVIIA (P01386) Protein Card

General Information
Name MVIIA
Alternative name(s) M7a,SNX-111,Ziconotide
Organism Conus magus (Magus cone)
Organism region Indo-Pacific
Organism diet piscivorous
Protein Type Wild type
Protein precursor MVIIA precursor (1564)
MVIIA precursor (3999)
Notes Mutation analysis and molecular calculation revealed that the toxicity of MVIIA mainly arose from Met12 in the loop 2, and this residue inserts into a hydrophobic hole (Ile300, Phe302 and Leu305) located between repeats II and III of Cav2.2. The combinative mutations of the loop 2 of MVIIA or other u-conopeptides may be used for future development of more effective Cav2.2 inhibitors with lower side effects Wang et al 2016.

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

Sequence
CKGKGAKCSRLMYDCCTGSCRSGKC(nh2)
Modified residues
positionsymbolname
26nh2C-term amidation
Sequence evidence protein level
Average Mass 2639.12
Monoisotopic Mass 2637.10
Isoelectric Point 12.02
Extinction Coefficient [280nm] 1490.00

Activity

IC50: Voltage-Gated Calcium Channels

TargetOrganismIC50nhillCompetitorRef
Cav2.1R. norvegicus156nMMVIICFavreau,P. et al. (2001)
440nMMVIICLewis,R.J. et al. (2000)
Cav2.2H. sapiens0.18 uM+/-0.031.17Wang,F. et al. (2016)
7.96nM+/-1.6Lee,S. et al. (2010)
R. norvegicus55pMGVIALewis,R.J. et al. (2000)
13pMMVIIAMiljanich,G.P. et al. (1993)
19pMGVIAMould,J. et al. (2004)

Percentage inhibition: Voltage-Gated Calcium Channels

TargetOrganism% inhibitionConcentrationRef
Cav2.1H. sapiens(Up to 10uM administered with no effect)0Wang,F. et al. (2016)

Synthetic variants
MVIIA With C-Terminal GlyCKGKGAKCSRLMYDCCTGSCRSGKCG
MVIIA[D14N]CKGKGAKCSRLMYNCCTGSCRSGKC(nh2)
MVIIA[G2A,K3A,A5K,K6P]CKAAGKPCSRLMYDCCTGSCRSGKC(nh2)
MVIIA[K2A]CAGKGAKCSRLMYDCCTGSCRSGKC(nh2)
MVIIA[L11I,M12A,D14N]CKGKGAKCSRIAYNCCTGSCRSGKC(nh2)
MVIIA[L11I]CKGKGAKCSRIMYDCCTGSCRSGKC(nh2)
MVIIA[M12A]CKGKGAKCSRLAYDCCTGSCRSGKC
MVIIA[R10K]CKGKGAKCSKLMYDCCTGSCRSGKC(nh2)
MVIIA[Y13A]CKGKGAKCSRLMADCCTGSCRSGKC(nh2)
MVIIA[Y13R]CKGKGAKCSRLMRDCCTGSCRSGKC
SNX-190CKGAGAKCSRLMYDCCTGSCRSGKC
SNX-191CAGKGAKCSRLMYDCCTGSCRSGKC
SNX-194CKGKGAKCSRL(Nle)YDCCTGSCRSGKC
SNX-195CKGKGAKCSRLMYDCCTGSCRSGAC
SNX-198CKGKGAKCSRLMYDCCTGSCASGKC
SNX-199CKGKGAKCSALMYDCCTGSCRSGKC
SNX-200CKGKGAACSRLMYDCCTGSCRSGKC
SNX-201CKGKGAKCRKTSYDCCTGSCRSGKC
SNX-220(Ac)CKGKGAKCSRLMYDCCTGSCRSGKC
SNX-257CKGKGAKCSRLMFDCCTGSCRSGKC
SNX-259CKGKGAKCSRLM(Ity)DCCTGSCRSGKC
SNX-273CKGKGAKCSRLAYDCCTGSCRSGKC
SNX-279CKGKGAKCSRL(Mox)YDCCTGSCRSGKC
SNX-288CKGKGAKCSRAMYDCCTGSCRSGKC
SNX-308CKGKGAKCSRLMYACCTGSCRSGKC

References
Olivera,B.M., Gray,W.R., Zeikus,R., McIntosh,J.M., Varga,J., Rivier,J., de Santos,V. and Cruz,L.J. (1985) Peptide neurotoxins from fish-hunting cone snails Science 230:1338-1343
Olivera,B.M., Cruz,L.J., de Santos,V., Lecheminant,G.W., Griffin,D., Zeikus,R.D., McIntosh,J.M., Galyean,R., Varga,J., Gray,W.R. and Rivier,J.E. (1987) Neuronal calcium channel antagonists. Discrimination between calcium channel subtypes using omega-conotoxin from Conus magus venom Biochemistry 26:2086-2090
Kohno,T., Kim,J.I., Kobayashi,K., Kodera,Y., Maeda,T. and Sato,K. (1995) Three-dimensional structure in solution of the calcium channel blocker omega-conotoxin MVIIA Biochemistry 34:10256-10265
Nielsen,K.J., Thomas,L., Lewis,R.J., Alewood,P.F. and Craik,D.J. (1996) A consensus structure for omega-conotoxins with different selectivities for voltage-sensitive calcium channel subtypes: comparison of MVIIA, SVIB and SNX-202 J. Mol. Biol. 263:297-310
Atkinson,R.A., Kieffer,B., Dejaegere,A., Sirockin,F. and Lefevre,J.F. (2000) Structural and dynamic characterization of omega-conotoxin MVIIA: the binding loop exhibits slow conformational exchange Biochemistry 39:3908-3919
Adams,D.J., Smith,A.B., Schroeder,C.I., Yasuda,T. and Lewis,R.J. (2003) Omega-conotoxin CVID inhibits a pharmacologically distinct voltage-sensitive calcium channel associated with transmitter release from preganglionic nerve terminals J. Biol. Chem. 278:4057-4062
Kim,J.I., Takahashi,M., Martin-Moutot,N., Seagar,M.J., Ohtake,A. and Sato,K. (1995) Tyr13 is essential for the binding of omega-conotoxin MVIIC to the P/Q-type calcium channel Biochem. Biophys. Res. Commun. 214:305-309
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
Miljanich,G.P., Bitner,R.S., Bowersox,S.S., Fox,J.A., Valentino,K.L., Yamashiro,D.H. and Tsubokawa,M. (1993) Method of reducing neuronal damage using omega conotoxin peptides Patent: US 5189020-A 29 23-FEB-1993; Neurex Corporation; Menlo Park, CA
Nadasdi L, Yamashiro D, Chung D, Tarczy-Hornoch K, Adriaenssens P, Ramachandran J. (1995) Structure-activity analysis of a Conus peptide blocker of N-type neuronal calcium channels. Biochemistry 34:8076-8081
Price-Carter,M. and Goldenberg,D.P. (1998) Roles of individual disulfide bonds in the stability and folding of an omega-conotoxin. Biochemistry 37:9851-9861
Miljanich,G.P., Bowersox,S.S., Fox,J.A., Valentino,K.L., Bitner,R.S. and Yamashiro,D.H. (1993) Compositions for Delayed Treatment of Ischemia-related Neuronal Damage. Patent: PCT/US92 09766; Classification, C07K 7/10, A61K 37/02.
Kapono,C.A., Thapa,P., Cabalteja,C.C., Guendisch,D., Collier,A.C. and Bingham,J.P. (2013) Conotoxin truncation as a post-translational modification to increase the pharmacological diversity within the milked venom of Conus magus. Toxicon
Wang,F., Yan,Z., Liu,Z., Wang,S., Wu,Q., Yu,S., Ding,J. and Dai,Q. (2016) Molecular basis of toxicity of N-type calcium channel inhibitor MVIIA. Neuropharmacology 101:137-145

Internal links
Protein Precursor MVIIA precursor (1564)
MVIIA precursor (3999)
Nucleic acids
Structure NMR STRUCTURE OF OMEGA-CONOTOXIN MVIIA: CONSTRAINTS ON DISULPHIDE BRIDGES
NMR STRUCTURE OF OMEGA-CONOTOXIN MVIIA: NO CONSTRAINTS ON DISULPHIDE BRIDGES
N-TYPE CALCIUM CHANNEL BLOCKER, OMEGA-CONOTOXIN MVIIA, NMR, 15 STRUCTURES
NMR STUDY OF OMEGA-CONOTOXIN MVIIA 1OMG 3
NMR SOLUTION STRUCTURE OF OMEGA-CONOTOXIN MVIIA, A N-TYPE CALCIUM CHANNEL BLOCKER

External links
Ncbi 1OMG_A, 1MVI_A, 1MVJ_A, 1TTK_A, 1DW4_A, 1DW5_A

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