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	position symbol name 26 nh2 C-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

Target	Organism	IC50		nhill	Competitor	Ref
Cav2.1	R. norvegicus	156nM			MVIIC	Favreau,P. et al. (2001)
		440nM			MVIIC	Lewis,R.J. et al. (2000)
Cav2.2	H. sapiens	0.18 uM	+/-0.03	1.17		Wang,F. et al. (2016)
		7.96nM	+/-1.6			Lee,S. et al. (2010)
	R. norvegicus	55pM			GVIA	Lewis,R.J. et al. (2000)
		13pM			MVIIA	Miljanich,G.P. et al. (1993)
		19pM			GVIA	Mould,J. et al. (2004)

Percentage inhibition: Voltage-Gated Calcium Channels

Target	Organism		% inhibition		Concentration	Ref
Cav2.1	H. sapiens	(Up to 10uM administered with no effect)	0			Wang,F. et al. (2016)

Synthetic variants

MVIIA With C-Terminal Gly	CKGKGAKCSRLMYDCCTGSCRSGKCG
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-190	CKGAGAKCSRLMYDCCTGSCRSGKC
SNX-191	CAGKGAKCSRLMYDCCTGSCRSGKC
SNX-194	CKGKGAKCSRL(Nle)YDCCTGSCRSGKC
SNX-195	CKGKGAKCSRLMYDCCTGSCRSGAC
SNX-198	CKGKGAKCSRLMYDCCTGSCASGKC
SNX-199	CKGKGAKCSALMYDCCTGSCRSGKC
SNX-200	CKGKGAACSRLMYDCCTGSCRSGKC
SNX-201	CKGKGAKCRKTSYDCCTGSCRSGKC
SNX-220	(Ac)CKGKGAKCSRLMYDCCTGSCRSGKC
SNX-257	CKGKGAKCSRLMFDCCTGSCRSGKC
SNX-259	CKGKGAKCSRLM(Ity)DCCTGSCRSGKC
SNX-273	CKGKGAKCSRLAYDCCTGSCRSGKC
SNX-279	CKGKGAKCSRL(Mox)YDCCTGSCRSGKC
SNX-288	CKGKGAKCSRAMYDCCTGSCRSGKC
SNX-308	CKGKGAKCSRLMYACCTGSCRSGKC

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

Tools

Please cite:
Kaas Q, Yu R, Jin AH, Dutertre S and Craik DJ. ConoServer: updated content, knowledge, and discovery tools in the conopeptide database. Nucleic Acids Research (2012) 40(Database issue):D325-30
Kaas Q, Westermann JC, Halai R, Wang CK and Craik DJ. ConoServer, a database for conopeptide sequences and structures. Bioinformatics (2008) 24(3):445-6

ConoServer is managed at the Institute of Molecular Bioscience IMB, Brisbane, Australia.

The database and computational tools found on this website may be used for academic research only, provided that it is referred to ConoServer, the database of conotoxins (http://www.conoserver.org) and the above reference is cited. For any other use please contact David Craik (d.craik@imb.uq.edu.au).

Contacts:
David Craik
Quentin Kaas

Last updated: Tuesday 29 September 2020