ImI (P00010) Protein Card

General Information
Name ImI
Organism Conus imperialis
Organism region Indo-Pacific
Organism diet vermivorous
Protein Type Wild type
Protein precursor ImI precursor (93)

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

Sequence
GCCSDPRCAWRC(nh2)
Modified residues
positionsymbolname
13nh2C-term amidation
Sequence evidence protein level
Average Mass 1351.55
Monoisotopic Mass 1350.48
Isoelectric Point 10.99
Extinction Coefficient [280nm] 5500.00

Activity

IC50: Nicotinic acetylcholine receptors

TargetOrganismIC50nhillAgonistRef
α1β1δεH. sapiens>10uM50nM AchEllison,M. et al. (2004)
α1β1γδM. musculus51uM500nM AchJohnson,D.S. et al. (1995)
α2β2H. sapiens>10uM100uM AchEllison,M. et al. (2004)
R. norvegicus>5uM300uM AchJohnson,D.S. et al. (1995)
α2β4H. sapiens>10uM100uM AchEllison,M. et al. (2004)
R. norvegicus>5uM300uM AchJohnson,D.S. et al. (1995)
α3β2H. sapiens40.8nM0.9100uM AchEllison,M. et al. (2004)
R. norvegicus>5uM300uM AchJohnson,D.S. et al. (1995)
α3β4H. sapiens3.39uM1.32100uM AchEllison,M. et al. (2004)
R. norvegicus>300uM300nM epibatidineArmishaw,C. et al. (2009)
>5uM300uM AchJohnson,D.S. et al. (1995)
α4β2H. sapiens>10uM100uM AchEllison,M. et al. (2004)
R. norvegicus>5uM300uM AchJohnson,D.S. et al. (1995)
α4β4H. sapiens>10uM100uM AchEllison,M. et al. (2004)
R. norvegicus>5uM300uM AchJohnson,D.S. et al. (1995)
α7H. sapiens595nM1.15200uM AchEllison,M. et al. (2004)
2.6uM30uM AchArmishaw,C. et al. (2009)
130nM+/-300.98500uM AchRogers,J.P. et al. (2000)
R. norvegicus220nM500uM AchJohnson,D.S. et al. (1995)
69nM+/-150.8200uM AchArmishaw,C.J. et al. (2006)
1.04uM+/-0.1250uM AchUtkin,Y.N. et al. (1999)
191 nM0.879 200uM AchEllison,M.A. and McIntosh,J.M. and Olivera,B.M. (2003)
α9R. norvegicus1.8uM100uM AchJohnson,D.S. et al. (1995)

Ki: Nicotinic acetylcholine receptors

TargetOrganismKiCompetitorAgonistRef
α1β1δεH. sapiens119uM+/-43.75nM 125 I-BgtxQuiram,P.A. and Sine,S.M. (1998)
α3β4R. norvegicus>100uM25 pM 3H-epibatidine5mM (S)-nicotineArmishaw,C. et al. (2009)
>100uM25 pM 3H-epibatidine5mM S-nicotineArmishaw,C. et al. (2009)
α7H. sapiens2.45uM+/-0.13.75nM 125 I-BgtxQuiram,P.A. and Sine,S.M. (1998)
α7-5HT3 chimaeraG. gallus4.0uM+/-0.35nM I-BgtxServent,D. et al. (1998)
H. sapiens2.38uM+/-0.053.75nM 125 I-BgtxQuiram,P.A. and Sine,S.M. (1998)
R. norvegicus1.2uM0.5nM 3H-methylcaconitine5mM S-nicotineArmishaw,C. et al. (2009)

Synthetic variants
Ac-ImI(nh2)CRWACRPDSCCG(Ac)
ImI [A9L,W10Y,R11ABA]C(ABA)YLCRPDSCCG
ImI [A9S](nh2)CRWACRPDSCCG
ImI [C2Agl,C8Agl](nh2)CRWA(Agl)RPDSC(Agl)G
ImI [C2U,C3U,C8U,C12U](nh2)URWAURPDSUUG
ImI [C2U,C8U](nh2)CRWAURPDSCUG
ImI [C3U,C12U](nh2)URWACRPDSUCG
ImI [D5A](nh2)CRWACRPASCCG
ImI [D5E](nh2)CRWACRPESCCG
ImI [D5K](nh2)CRWACRPKSCCG
ImI [D5N](nh2)CRWACRPNSCCG
ImI [D5R,R7D](nh2)CRWACDPRSCCG
ImI [G1A](nh2)CRWACRPDSCCA
ImI [P60](nh2)CRWACRODSCCG
ImI [P6A(S)Pro](nh2)CRWACR(A(S)Pro)DSCCG
ImI [P6APro](nh2)CRWACR(APro)DSCCG
ImI [P6A](nh2)CRWACRADSCCG
ImI [P6G](nh2)CRWACRGDSCCG
ImI [P6K](nh2)CRWACRKDSCCG
ImI [P6K] deamidatedCRWACRKDSCCG
ImI [P6S](nh2)CRWACRSDSCCG
ImI [P6V](nh2)CRWACRVDSCCG
ImI [P6benzPro](nh2)CRWACR(benz-Pro)DSCCG
ImI [P6betPro](nh2)CRWACR(bet-Pro)DSCCG
ImI [P6fluo(S)Pro](nh2)CRWACR(F-(S)-Pro)DSCCG
ImI [P6fluoPro](nh2)CRWACR(F-Pro)DSCCG
ImI [P6guaPro](nh2)CRWACR(Gua-Pro)DSCCG
ImI [P6naphPro](nh2)CRWACR(naph-Prot)DSCCG
ImI [P6phi(3S)Pro](nh2)CRWACR(phi3-Pro)DSCCG
ImI [P6phi(5R)Pro](nh2)CRWACR(phi5-Pro)DSCCG
ImI [P6phi(S)Pro](nh2)CRWACR(phi-(S)-Pro)DSCCG
ImI [P6phiPro](nh2)CRWACR(phi-Pro)DSCCG
ImI [R11A](nh2)CAWACRPDSCCG
ImI [R11E](nh2)CEWACRPDSCCG
ImI [R11Q](nh2)CQWACRPDSCCG
ImI [R7A](nh2)CRWACAPDSCCG
ImI [R7E](nh2)CRWACEPDSCCG
ImI [R7K](nh2)CRWACKPDSCCG
ImI [R7L](nh2)CRWACLPDSCCG
ImI [R7Nle](nh2)CRWAC(Nle)PDSCCG
ImI [R7Q](nh2)CRWACQPDSCCG
ImI [S4A](nh2)CRWACRPDACCG
ImI [W10A](nh2)CRAACRPDSCCG
ImI [W10F](nh2)CRFACRPDSCCG
ImI [W10T](nh2)CRTACRPDSCCG
ImI [W10Y](nh2)CRYACRPDSCCG
ImI deamidatedCRWACRPDSCCG
Imi1(nh2)CRWACRPDSA(L-Dtn)G

References
McIntosh,J.M., Yoshikami,D., Mahe,E., Nielsen,D.B., Rivier,J.E., Gray,W.R. and Olivera,B.M. (1994) A nicotinic acetylcholine receptor ligand of unique specificity, alpha-conotoxin ImI J. Biol. Chem. 269:16733-16739
Servent,D., Lamthanh,H., Antil,S., Bertrand,D., Corringer,P.J., Changeux,J.P. and Menez,A. (1998) Functional Determinants By Which Snake And Cone Snail Toxins Block The Alpha 7 Neuronal Nicotinic Acetylcholine Receptors J.Physiol. Paris 92:107-111
Quiram,P.A. and Sine,S.M. (1998) Identification of residues in the neuronal alpha7 acetylcholine receptor that confer selectivity for conotoxin ImI J. Biol. Chem. 273:11001-11006
Maslennikov,I.V., Shenkarev,Z.O., Zhmak,M.N., Ivanov,V.T., Methfessel,C., Tsetlin,V.I. and Arseniev,A.S. (1999) NMR spatial structure of alpha-conotoxin ImI reveals a common scaffold in snail and snake toxins recognizing neuronal nicotinic acetylcholine receptors FEBS Lett. 444:275-280
Rogers,J.P., Luginbuhl,P., Shen,G.S., McCabe,R.T., Stevens,R.C. and Wemmer,D.E. (1999) NMR solution structure of alpha-conotoxin ImI and comparison to other conotoxins specific for neuronal nicotinic acetylcholine receptors Biochemistry 38:3874-3882
Lamthanh,H., Jegou-Matheron,C., Servent,D., Menez,A. and Lancelin,J.M. (1999) Minimal conformation of the alpha-conotoxin ImI for the alpha7 neuronal nicotinic acetylcholine receptor recognition: correlated CD, NMR and binding studies FEBS Lett. 454:293-298
Johnson,D.S., Martinez,J., Elgoyhen,A.B., Heinemann,S.F. and McIntosh,J.M. (1995) alpha-Conotoxin ImI exhibits subtype-specific nicotinic acetylcholine receptor blockade: preferential inhibition of homomeric alpha 7 and alpha 9 receptors Mol. Pharmacol. 48:194-199
Ellison,M.A., McIntosh,J.M. and Olivera,B.M. (2003) alpha-Conotoxins ImI and ImII: similar alpha 7 nicotinic receptor antagonists act at different sites J. Biol. Chem. 278:757-764
Gehrmann,J., Daly,N.L., Alewood,P.F. and Craik,D.J. (1999) Solution structure of alpha-conotoxin ImI by 1H nuclear magnetic resonance J. Med. Chem. 42:2364-2372
Hansen,S.B., Sulzenbacher,G., Huxford,T., Marchot,P., Taylor,P. and Bourne,Y. (2005) Structures Of Aplysia Achbp Complexes With Nicotinic Agonists And Antagonists Reveal Distinctive Binding Interfaces And Conformations Embo J. 24:3635
Ulens,C., Hogg,R.C., Celie,P.H., Bertrand,D., Tsetlin,V., Smit,A.B. and Sixma,T.K. (2006) Structural determinants of selective alpha-conotoxin binding to a nicotinic acetylcholine receptor homolog AChBP Proc. Natl. Acad. Sci. U.S.A. 103:3615-3620
Armishaw,C.J., Daly,N.L., Nevin,S.T., Adams,D.J., Craik,D.J. and Alewood,P.F. (2006) Alpha-selenoconotoxins, a new class of potent alpha7 neuronal nicotinic receptor antagonists J. Biol. Chem. 281:14136-14143
Ellison,M., Gao,F., Wang,H.L., Sine,S.M. and Olivera,B.M. (2004) Alpha-conotoxins ImI and ImII target distinct regions of the human alpha7 nicotinic acetylcholine receptor and distinguish human nicotinic receptor subtypes. Biochemistry 43:16019-16026
Yu,R., Craik,D.J. and Kaas,Q. (2011) Blockade of neuronal α7-nAChR by α-conotoxin ImI explained by computational scanning and energy calculations. PLoS Comput. Biol. 7
Armishaw,C., Jensen,A.A., Balle,T., Clark,R.J., Harpsøe,K., Skonberg,C., Liljefors,T. and Strømgaard,K. (2009) Rational design of alpha-conotoxin analogues targeting alpha7 nicotinic acetylcholine receptors: improved antagonistic activity by incorporation of proline derivatives. J. Biol. Chem. 284:9498-9512
Armishaw,C.J., Singh,N., Medina-Franco,J.L., Clark,R.J., Scott,K.C., Houghten,R.A. and Jensen,A.A. (2010) A synthetic combinatorial strategy for developing alpha-conotoxin analogs as potent alpha7 nicotinic acetylcholine receptor antagonists. J. Biol. Chem. 285:1809-1821
Utkin,Y.N., Zhmak,M.N., Methfessel,C. and Tsetlin,V.I. (1999) Aromatic substitutions in alpha-conotoxin ImI. Synthesis of iodinated photoactivatable derivative. Toxicon 37:1683-1695
Yu,R., Kaas,Q. and Craik,D.J. (2012) Delineation of the unbinding pathway of α-conotoxin ImI from the α7 nicotinic acetylcholine receptor. J Phys Chem B 116:6097-6105

Internal links
Protein Precursor ImI precursor (93)
Nucleic acids
Structure MINIMAL CONFORMATION OF THE ALPHA-CONOTOXIN IMI FOR THE ALPHA7 NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR RECOGNITION
SOLUTION STRUCTURE OF ALPHA-CONOTOXIN IM1
ALPHA-CONOTOXIN IMI
NMR SOLUTION STRUCTURE OF ALPHA-CONOTOXIN IM1, 20 STRUCTURES
CRYSTAL STRUCTURE OF APLYSIA CALIFORNICA ACHBP IN COMPLEX WITH ALPHA-CONOTOXIN IMI
CRYSTAL STRUCTURE OF ACETYLCHOLINE BINDING PROTEIN (ACHBP) FROM APLYSIA CALIFORNICA IN COMPLEX WITH ALPHA-CONOTOXIN IMI

External links
Ncbi 1IMI_A, 2C9T_T, 2C9T_S, 2C9T_R, 2C9T_Q, 2C9T_P, 2C9T_O, 2C9T_M, 2C9T_K, 1IM1_A, 2BYP_F, 1G2G_A, 1CNL_A

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