Conantokin-G (P01338) Protein Card

General Information
Name Conantokin-G
Alternative name(s) CGX-1007,Con-G,sleeper
Organism Conus geographus (Geography cone)
Organism region Indo-Pacific
Organism diet piscivorous
Protein Type Wild type
Protein precursor Conantokin-G precursor (variant) (1353)
Conantokin-G precursor (1373)
Notes Conantokin-G is active against the NMDA glutamate receptors, and more precisely a NR2B-selective competitive antagonist (Donevan and McCabe 2000).

Classification
Conopeptide class conantokin
Gene superfamily B1 superfamily
Pharmacological family

Sequence
GE(Gla)(Gla)LQ(Gla)NQ(Gla)LIR(Gla)KSN(nh2)
Modified residues
positionsymbolname
3GlaGamma carboxylic glutamic acid
4GlaGamma carboxylic glutamic acid
7GlaGamma carboxylic glutamic acid
10GlaGamma carboxylic glutamic acid
14GlaGamma carboxylic glutamic acid
18nh2C-term amidation
Sequence evidence protein level
Average Mass 2264.21
Monoisotopic Mass 2262.94
Isoelectric Point 2.02
Extinction Coefficient [280nm] NA

Activity

IC50: Ionotropic glutamate receptors

TargetOrganismIC50AgonistRef
GluN2AR. norvegicus>10uM200uM glutamateTeichert,R.W. et al. (2007)
GluN2BR. norvegicus0.1uM 200uM glutamateTeichert,R.W. et al. (2007)
GluN2CR. norvegicus1uM200uM glutamateTeichert,R.W. et al. (2007)
GluN2DR. norvegicus1uM 200uM glutamateTeichert,R.W. et al. (2007)

Synthetic variants
Conantokin-G[+10Gla,Gla10Buc,Gla14Buc]GE(Gla)(Gla)LQ(Gla)NQ(Gla)(Buc)LIR(Buc)KSN(nh2)
Conantokin-G[Gla10Bsc,Gla14Bsc]GE(Gla)(Gla)LQ(Gla)NQ(Bsc)LIR(Bsc)KSN(nh2)
Conantokin-G[Gla10Buc,Gla14Buc]GE(Gla)(Gla)LQ(Gla)NQ(Buc)LIR(Buc)KSN(nh2)
Conantokin-G[Gla7Buc,Gla14Buc]GE(Gla)(Gla)LQ(Huc)NQ(Gla)LIR(Buc)KSN(nh2)

References
Malmberg,A.B., Gilbert,H., McCabe,R.T. and Basbaum,A.I. (2003) Powerful antinociceptive effects of the cone snail venom-derived subtype-selective NMDA receptor antagonists conantokins G and T Pain 101:109-116
Skjaerbaek,N., Nielsen,K.J., Lewis,R.J., Alewood,P. and Craik,D.J. (1997) Determination of the solution structures of conantokin-G and conantokin-T by CD and NMR spectroscopy J. Biol. Chem. 272:2291-2299
Rigby,A.C., Baleja,J.D., Furie,B.C. and Furie,B. (1997) Three-dimensional structure of a gamma-carboxyglutamic acid-containing conotoxin, conantokin G, from the marine snail Conus geographus: the metal-free conformer Biochemistry 36:6906-6914
Rigby,A.C., Baleja,J.D., Li,L., Pedersen,L.G., Furie,B.C. and Furie,B. (1997) Role of gamma-carboxyglutamic acid in the calcium-induced structural transition of conantokin G, a conotoxin from the marine snail Conus geographus Biochemistry 36:15677-15684
McIntosh,J.M., Olivera,B.M., Cruz,L.J. and Gray,W.R. (1984) Gamma-carboxyglutamate in a neuroactive toxin J. Biol. Chem. 259:14343-14346
Williams,A.J., Dave,J.R., Phillips,J.B., Lin,Y. and Tortella,F.C. (2000) Neuroprotective efficacy and therapeutic window of the high-affinity N-methyl-D-aspartate antagonist conantokin-G: in vitro (primary cerebellar neurons) and in vivo (rat model of transient focal brain ischemia) studies. J. Pharmacol. Exp. Ther. 294:378-386
Williams,A.J., Ling,G. and Tortella,F.C. (2002) Intrathecal CGX-1007 is neuroprotective in a rat model of focal cerebral ischemia. Neuroreport 13:821-824
Williams,A.J., Ling,G., Berti,R., Moffett,J.R., Yao,C., Lu,X.M. and Tortella,F.C. (2003) Treatment with the snail peptide CGX-1007 reduces DNA damage and alters gene expression of c-fos and bcl-2 following focal ischemic brain injury in rats. Exp Brain Res 153:16-26
Donevan,S.D. and McCabe,R.T. (2000) Conantokin G is an NR2B-selective competitive antagonist of N-methyl-D-aspartate receptors. Mol. Pharmacol. 58:614-623
Olivera BM, McIntosh JM, Clark C, Middlemas D, Gray WR, Cruz LJ. (1985) A sleep-inducing peptide from Conus geographus venom. Toxicon 23:277-282
Balsara,R., Li,N., Weber-Adrian,D., Huang,L. and Castellino,F.J. (2012) Opposing action of conantokin-G on synaptically and extrasynaptically-activated NMDA receptors. Neuropharmacology 62:2227-2238

Internal links
Protein Precursor Conantokin-G precursor (variant) (1353)
Conantokin-G precursor (1373)
Nucleic acids
Structure NMR STRUCTURE OF METAL-FREE CONANTOKIN G, 1 STRUCTURE
NMDA RECEPTOR ANTAGONIST, CONANTOKIN-G, NMR, 17 STRUCTURES
NMR STRUCTURE OF CALCIUM BOUND CONFORMER OF CONANTOKIN G, MINIMIZED AVERAGE STRUCTURE

External links
Ncbi 1AWY_A, 1AD7_A, 1ONU_A

Tools