PnIA [sTy15Y] (P04377) Protein Card

General Information

Name	PnIA [sTy15Y]
Alternative name(s)	PnIA,PnIA[Y(SO₃)15Y]-NH₂
Organism	synthetic construct
Protein Type	Synthetic
Parent	PnIA

Classification

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

Sequence

GCCSLPPCAANNPDYC(nh2)

Modified residues

position	symbol	name
17	nh2	C-term amidation

Average Mass

1622.81

Monoisotopic Mass

1621.58

Isoelectric Point

5.47

Extinction Coefficient [280nm]

1490.00

Activity

IC50: Nicotinic acetylcholine receptors

Target	Organism	IC50		n_hill	Agonist	Ref
α3β2	R. norvegicus	9.56nM		1	300uM Ach	Luo,S. et al. (1999)
	Unknown	7.74nM	[6.79-8.81]	0.85	100uM Ach	Dutertre,S. et al. (2005)
α4β2	Unknown	>10uM			100uM Ach	Dutertre,S. et al. (2005)
α6/α3β2β3	H. sapiens	2.8 nM	[2-3.8]		ACh(100 uM)	Hone et al. (2018)
	R. norvegicus	3.3 nM	[3-3.6]		ACh(100 uM)	Hone et al. (2018)
α6/α3β4	H. sapiens	149 nM	[135-164]		ACh(300 uM)	Hone et al. (2018)
	R. norvegicus	8456 nM	[5419-13290]		300uM Ach	Hone et al. (2018)
α7	G. gallus	349nM			200uM Ach	Hogg,R.C. et al. (2003)
	R. norvegicus	252nM		1.2	1mM Ach	Luo,S. et al. (1999)

Kd: Nicotinic acetylcholine receptors

Target	Organism	Kd		Ref
α7	R. norvegicus	176nM		Luo,S. et al. (1999)

Ki: Nicotinic acetylcholine receptors

Target	Organism	Ki		Competitor	Ref
AChBP	A. californica	1.41 nM	[1.1-1.7]	1 nM [³H]-epibatidine	Ho,T.N.T. et al. (2021)
	L. stagnalis	9.12 uM	[3.24-26.92]	1 nM [³H]-epibatidine	Ho,T.N.T. et al. (2021)
		1000 nM	+/-300	I-Bgt(10 uM)	Dutertre,S. et al. (2007)

References

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

Dutertre,S., Ulens,C., Büttner,R., Fish,A., van Elk,R., Kendel,Y., Hopping,G., Alewood,P.F., Schroeder,C., Nicke,A., Smit,A.B., Sixma,T.K. and Lewis,R.J. (2007) AChBP-targeted alpha-conotoxin correlates distinct binding orientations with nAChR subtype selectivity. EMBO J. 26:3858-3867

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

Hone, A.J., Talley, T.T., Bobango, J., Melo, C.H., Hararah, F., Gajewiak, J., Christensen, S., Harvey, P.J., Craik, D.J. and McIntosh, J.M. (2018) Molecular determinants of α-conotoxin potency for inhibition of human and rat α6β4 nicotinic acetylcholine receptors Journal of Biological Chemistry 293:17838-17852

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

External links

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