PnIA (P00051) Protein Card

General Information
Name PnIA
Alternative name(s) Pn1a
Organism Conus pennaceus
Organism region Indo-Pacific
Organism diet molluscivorous
Protein Type Wild type
Notes The presence of a sulfotyrosine was discovered in 1999, while PnIA was isolated from the venom in 1994. There is some confusion in the literature regarding the use of PnIA with sulfotyrosine or of a synthetic version without it. See activity of PnIA [sTy15Y].

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

Sequence
GCCSLPPCAANNPD(sTy)C(nh2)
Modified residues
positionsymbolname
15sTySulfotyrosine
17nh2C-term amidation
Sequence evidence protein level
Average Mass 1701.86
Monoisotopic Mass 1700.53
Isoelectric Point 2.19
Extinction Coefficient [280nm] 1490.00

Activity

IC50: Nicotinic acetylcholine receptors

TargetOrganismIC50AgonistRef
α3β4R. norvegicus>300uM300nM epibatidineArmishaw,C. et al. (2009)
α7H. sapiens510nM30uM AchArmishaw,C. et al. (2009)

Ki: Nicotinic acetylcholine receptors

TargetOrganismKiCompetitorAgonistRef
α3β4R. norvegicus>100uM25 pM 3H-epibatidine5mM (S)-nicotineArmishaw,C. et al. (2009)
α7-5HT3 chimaeraR. norvegicus260nM0.5nM 3H-methylcaconitine5mM S-nicotineArmishaw,C. et al. (2009)

Synthetic variants
PnIA [A10L,D14K,sTy15Y](nh2)CYKPNNLACPPLSCCG
PnIA [A10L,sTy15Y](nh2)CYDPNNLACPPLSCCG
PnIA [L5R,A10L](nh2)C(sTy)DPNNLACPPRSCCG
PnIA [N11S,sTy15Y](nh2)CYDPNSAACPPLSCCG
PnIA [P6A(S)Pro](nh2)C(sTy)DPNNAACP(A(S)Pro)LSCCG
PnIA [P6APro](nh2)C(sTy)DPNNAACP(APro)LSCCG
PnIA [P6O](nh2)C(sTy)DPNNAACPOLSCCG
PnIA [P6benzPro](nh2)C(sTy)DPNNAACP(benz-Pro)LSCCG
PnIA [P6betPro](nh2)C(sTy)DPNNAACP(bet-Pro)LSCCG
PnIA [P6fluo(S)Pro](nh2)C(sTy)DPNNAACP(F-(S)-Pro)LSCCG
PnIA [P6fluoPro](nh2)C(sTy)DPNNAACP(F-Pro)LSCCG
PnIA [P6guaPro](nh2)C(sTy)DPNNAACP(Gua-Pro)LSCCG
PnIA [P6naphPro](nh2)C(sTy)DPNNAACP(naph-Prot)LSCCG
PnIA [P6phi(3S)Pro](nh2)C(sTy)DPNNAACP(phi3-Pro)LSCCG
PnIA [P6phi(5R)Pro](nh2)C(sTy)DPNNAACP(phi5-Pro)LSCCG
PnIA [P6phi(S)Pro](nh2)C(sTy)DPNNAACP(phi-(S)-Pro)LSCCG
PnIA [P6phiPro](nh2)C(sTy)DPNNAACP(phi-Pro)LSCCG
PnIA [R5,R9,L10,R14](nh2)YRPNNLRCPPRSCCG
PnIA [R9,L10](nh2)YDPNNLRCPPLSCCG
PnIA [R9](nh2)YDPNNARCPPLSCCG
PnIA [sTy15Y](nh2)CYDPNNAACPPLSCCG
Pni1(nh2)CYDPNNAACPPLSCCG

References
Fainzilber,M., Hasson,A., Oren,R., Burlingame,A.L., Gordon,D., Spira,M.E. and Zlotkin,E. (1994) New mollusc-specific alpha-conotoxins block Aplysia neuronal acetylcholine receptors Biochemistry 33:9523-9529
Wolfender,J.L., Chu,F., Ball,H., Wolfender,F., Fainzilber,M., Baldwin,M.A. and Burlingame,A.L. (1999) Identification of tyrosine sulfation in Conus pennaceus conotoxins alpha-PnIA and alpha-PnIB: further investigation of labile sulfo- and phosphopeptides by electrospray, matrix-assisted laser desorption/ionization (MALDI) and atmospheric pressure MALDI mass spectrometry J Mass Spectrom 34:447-454
Luo,S., Nguyen,T.A., Cartier,G.E., Olivera,B.M., Yoshikami,D. and McIntosh,J.M. (1999) Single-residue alteration in alpha-conotoxin PnIA switches its nAChR subtype selectivity Biochemistry 38:14542-14548
Hu,S.H., Gehrmann,J., Guddat,L.W., Alewood,P.F., Craik,D.J. and Martin,J.L. (1996) The 1.1 A crystal structure of the neuronal acetylcholine receptor antagonist, alpha-conotoxin PnIA from Conus pennaceus Structure 4:417-423
Hogg,R.C., Miranda,L.P., Craik,D.J., Lewis,R.J., Alewood,P.F. and Adams,D.J. (1999) Single amino acid substitutions in alpha-conotoxin PnIA shift selectivity for subtypes of the mammalian neuronal nicotinic acetylcholine receptor. J. Biol. Chem. 274:36559-36564
Hogg,R.C., Hopping,G., Alewood,P.F., Adams,D.J. and Bertrand,D. (2003) Alpha-conotoxins PnIA and [A10L]PnIA stabilize different states of the alpha7-L247T nicotinic acetylcholine receptor. J. Biol. Chem. 278:26908-26914
Dutertre,S., Nicke,A., and Lewis,R.J. (2005) Beta2 subunit contribution to 4/7 alpha-conotoxin binding to the nicotinic acetylcholine receptor. J. Biol. Chem. 280:30460-30468

Internal links
Nucleic acids
Structure

External links
UniProtKB/Swiss-Prot P50984
Ncbi P50984, AAB31731

Tools