Peptide Information

General Information of This Peptide
Peptide ID
BTDP006018
Peptide Name
Alpha-conotoxin PnIA
Symonym
Alpha-PnIA
Species
Conus pennaceus (Feathered cone) (Conus episcopus)
Uniprot Name
CA1A_CONPE
Alphafold ID
P50984
3D Structure
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2D Sequence
3D Structure
Source
RSCB PDB: 1PEN
Sequence
GCCSLPPCAANNPDYC
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Sequence Length
16
Mass (Da)
1628
Sequence Removed Signal Peptide
GCCSLPPCAANNPDYC
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Disulfide Bond
2-8;3-16
PDB ID
1PEN , 2BR8 , 7N1Z
        Click to Show/Hide the Complete Species Lineage
Kingdom: Metazoa
Phylum: Mollusca
Class: Gastropoda
Order: Neogastropoda
Family: Conidae
Genus: Conus
Species: Conus pennaceus
Full List of Activity Data of This Peptide Toxin
                        Target Name Activity Data Type Activity Data Concentration Note Reference
 Target Info    nAChR alpha-6-beta-4 IC50
>500 nM
 .
Replacement of Ala-10 by a norleucine (A10Nle)
[1- 13]
 Target Info    nAChR alpha-3-beta-2 IC50
0.7 nM
 .
Replacement of Ala-10 by a norleucine (A10Nle)
[1- 13]
 Target Info    nAChR alpha-7 IC50
4.3 nM
 .
Replacement of Ala-10 by a norleucine (A10Nle)
[1- 13]
 Target Info    nAChR alpha-3-beta-2 IC50
7.68 nM
 .
Replacement of Ala-10 by a norleucine (A10Nle)
[1- 13]
 Target Info    nAChR alpha-6/alpha-3-beta-2-beta-3 IC50
11 nM
 .
Replacement of Ala-10 by a norleucine (A10Nle)
[1- 13]
 Target Info    nAChR alpha-7 IC50
253 nM
 .
Replacement of Ala-10 by a norleucine (A10Nle)
[1- 13]
References
Ref 1 New mollusc-specific alpha-conotoxins block Aplysia neuronal acetylcholine receptors. Biochemistry. 1994 Aug 16;33(32):9523-9. doi: 10.1021/bi00198a018.
Ref 2 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. 1999 Apr;34(4):447-54. doi: 10.1002/(SICI)1096-9888(199904)34:4<447::AID-JMS801>3.0.CO;2-1.
Ref 3 Single-residue alteration in alpha-conotoxin PnIA switches its nAChR subtype selectivity. Biochemistry. 1999 Nov 2;38(44):14542-8. doi: 10.1021/bi991252j.
Ref 4 Identification of residues that confer alpha-conotoxin-PnIA sensitivity on the alpha 3 subunit of neuronal nicotinic acetylcholine receptors. J Pharmacol Exp Ther. 2003 Aug;306(2):664-70. doi: 10.1124/jpet.103.051656. Epub 2003 May 6.
Ref 5 Beta2 subunit contribution to 4/7 alpha-conotoxin binding to the nicotinic acetylcholine receptor. J Biol Chem. 2005 Aug 26;280(34):30460-8. doi: 10.1074/jbc.M504229200. Epub 2005 Jun 1.
Ref 6 AChBP-targeted alpha-conotoxin correlates distinct binding orientations with nAChR subtype selectivity. EMBO J. 2007 Aug 22;26(16):3858-67. doi: 10.1038/sj.emboj.7601785. Epub 2007 Jul 26.
Ref 7 Rational design of alpha-conotoxin analogues targeting alpha7 nicotinic acetylcholine receptors: improved antagonistic activity by incorporation of proline derivatives. J Biol Chem. 2009 Apr 3;284(14):9498-512. doi: 10.1074/jbc.M806136200. Epub 2009 Jan 8.
Ref 8 Nicotinic acetylcholine receptors in dorsal root ganglion neurons include the 64* subtype. FASEB J. 2012 Feb;26(2):917-26. doi: 10.1096/fj.11-195883. Epub 2011 Oct 24.
Ref 9 Hydrophobic residues at position 10 of -conotoxin PnIA influence subtype selectivity between 7 and 32 neuronal nicotinic acetylcholine receptors. Biochem Pharmacol. 2014 Oct 15;91(4):534-42. doi: 10.1016/j.bcp.2014.07.025. Epub 2014 Aug 5.
Ref 10 Species specificity of rat and human 7 nicotinic acetylcholine receptors towards different classes of peptide and protein antagonists. Neuropharmacology. 2018 Sep 1;139:226-237. doi: 10.1016/j.neuropharm.2018.07.019. Epub 2018 Jul 17.
Ref 11 -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. 2020 Apr 7;18(4):193. doi: 10.3390/md18040193.
Ref 12 The 1.1 A crystal structure of the neuronal acetylcholine receptor antagonist, alpha-conotoxin PnIA from Conus pennaceus. Structure. 1996 Apr 15;4(4):417-23. doi: 10.1016/s0969-2126(96)00047-0.
Ref 13 Posttranslational modifications of -conotoxins: sulfotyrosine and C-terminal amidation stabilise structures and increase acetylcholine receptor binding. RSC Med Chem. 2021 Jul 26;12(9):1574-1584. doi: 10.1039/d1md00182e. eCollection 2021 Sep 23.
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