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].

Osipov et al.,2020 reported that PnIA inhibits Ehrlich carcinoma growth and increase mouse survival.


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]GCCSLPPCALNNPKYC(nh2)
PnIA [A10L,sTy15Y]GCCSLPPCALNNPDYC(nh2)
PnIA [A9R,A10L]GCCSLPPCRLNNPDYC(nh2)
PnIA [A9R]GCCSLPPCRANNPDYC(nh2)
PnIA [L5R,A10L,sTy15Y]GCCSRPPCALNNPDYC(nh2)
PnIA [L5R,A9R,A10L,D14R]GCCSRPPCRLNNPRYC(nh2)
PnIA [N11S,sTy15Y]GCCSLPPCAASNPDYC(nh2)
PnIA [P6A(S)Pro]GCCSL(A(S)Pro)PCAANNPD(sTy)C(nh2)
PnIA [P6APro]GCCSL(APro)PCAANNPD(sTy)C(nh2)
PnIA [P6O]GCCSLOPCAANNPD(sTy)C(nh2)
PnIA [P6benzPro]GCCSL(benz-Pro)PCAANNPD(sTy)C(nh2)
PnIA [P6betPro]GCCSL(bet-Pro)PCAANNPD(sTy)C(nh2)
PnIA [P6fluo(S)Pro]GCCSL(F-(S)-Pro)PCAANNPD(sTy)C(nh2)
PnIA [P6fluoPro]GCCSL(F-Pro)PCAANNPD(sTy)C(nh2)
PnIA [P6guaPro]GCCSL(Gua-Pro)PCAANNPD(sTy)C(nh2)
PnIA [P6naphPro]GCCSL(naph-Prot)PCAANNPD(sTy)C(nh2)
PnIA [P6phi(3S)Pro]GCCSL(phi3-Pro)PCAANNPD(sTy)C(nh2)
PnIA [P6phi(5R)Pro]GCCSL(phi5-Pro)PCAANNPD(sTy)C(nh2)
PnIA [P6phi(S)Pro]GCCSL(phi-(S)-Pro)PCAANNPD(sTy)C(nh2)
PnIA [P6phiPro]GCCSL(phi-Pro)PCAANNPD(sTy)C(nh2)
PnIA [sTy15Y]GCCSLPPCAANNPDYC(nh2)
Pni1GCCSLPPCAANNPDYC(nh2)

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
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
Osipov,A.V., Terpinskaya,T.I., Yanchanka,T., Balashevich,T., Zhmak,M.N., Tsetlin,V.I. and Utkin,Y.N (2020) α-Conotoxins Enhance both the In Vivo Suppression of Ehrlich carcinoma Growth and In Vitro Reduction in Cell Viability Elicited by Cyclooxygenase and Lipoxygenase Inhibitors Mar Drugs 18

Internal links
Nucleic acids
Structure

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

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