PnIA (P00051) Protein Card

General Information
Name PnIA
Alternative name(s) Pn1a,PnIA-NH2
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.

  • PnIA promotes the proliferation of glioma C6 cells (Terpinskaya et al., 2021).

    • 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)
    AChBPA. californica1.20 nM[0.89-1.58]1 nM [3H]-epibatidineHo,T.N.T. et al. (2021)
    L. stagnalis3.80 uM[0.62-20.89]1 nM [3H]-epibatidineHo,T.N.T. et al. (2021)

    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)
    PnIA [sTy15Y]-OHGCCSLPPCAANNPDYC
    PnIA-OHGCCSLPPCAANNPD(sTy)C
    PnIA[A10L]GCCSLPPCALNNPDYC(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
    Terpinskaya,T.I., Osipov,A.V., Kryukova,E.V., Kudryavtsev,D.S., Kopylova,N.V., Yanchanka,T.L., Palukoshka,A.F., Gondarenko,E.A., Zhmak,M.N., Tsetlin,V.I. and Utkin,Y.N. (2021) α-Conotoxins and α-Cobratoxin Promote, while Lipoxygenase and Cyclooxygenase Inhibitors Suppress the Proliferation of Glioma C6 Cells. Mar Drugs 19
    Ho,T.N.T., Lee,H.S., Swaminathan,S., Goodwin,L., Rai,N., Ushay,B., Lewis,R.J. and Conibear,A.C. (2021) Posttranslational modifications of α-conotoxins: sulfotyrosine and C-terminal amidation stabilise structures and increase acetylcholine receptor binding. RSC Med Chem 12:1574-1584

    Internal links
    Nucleic acids
    Structure NMR structure of native PnIA

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

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