TxIA[A10L] (P08958) Protein Card

General Information

Name	TxIA[A10L]
Alternative name(s)	gTxIA[A10L]
Organism	synthetic construct
Protein Type	Synthetic
Parent	TxIA
Notes	By comparing the structures of α-conotoxins in complex with Ac-AChBP and by modelling α-conotoxins in complex with nAChRs, Lin et al. (2016) indicated that (i) Asn-11 and Asn-12 are key residues for binding to Ac-AChBP; (ii) Arg-5 is responsible for the selectivity for the Ac-AChBP principal site; (iii) Leu-10 is responsible for the selectivity for the Ac-AChBP complementary side.

Classification

Conopeptide class	conotoxin
Gene superfamily
Cysteine framework	I
Pharmacological family

Sequence

GCCSRPPCILNNPDLC(nh2)

Modified residues

position	symbol	name
17	nh2	C-term amidation

Sequence evidence

protein level

Average Mass

1699.99

Monoisotopic Mass

1698.71

Isoelectric Point

7.00

Extinction Coefficient [280nm]

Activity

IC50: Nicotinic acetylcholine receptors

Target	Organism		IC50		n_hill	Agonist	Ref
α3β2	R. norvegicus		2.0 nM	[1.8-2.4]		Ach	Dutertre,S. et al. (2007)
		(mutant ?3(I186R)?2)	76.5 nM	[58.9-99.3]	-1.261	100 uM ACh	Beissner,M. et al. (2012)
α4β2	R. norvegicus	(mutant ô°€?4(R185I)ô°?2(V109G)ô°)	6.6 nM	[4.8-9.1]	-0.755	100 uM ACh	Beissner,M. et al. (2012)
		(mutant ô°€?4(R185I)	3.2 nM	[2.6-3.8]	-1.11	100 uM ACh	Beissner,M. et al. (2012)
		(P195Q)ô°?2)	415 nM	[333-515]	-0.98	100 uM ACh	Beissner,M. et al. (2012)
		(mutant ô°€?4(R185A)ô°?2)	123 nM	[102-113]	-0.835	100 uM ACh	Beissner,M. et al. (2012)
		(mutant ô°€?4(R185I)ô°?2)	91.8 nM	[74.8-113]	-1.079	100 uM ACh	Beissner,M. et al. (2012)
		(mutant ô°€?4(R185E)ô°?2)	213 nM	[167-271]	-1.031	100 uM ACh	Beissner,M. et al. (2012)
		(mutant ô°€?4?2(V109G)ô°)	707 nM	[533-939]	-0.88	100 uM ACh	Beissner,M. et al. (2012)
α7	H. sapiens		0.50 uM	+/-0.04		30 uM choline	Ho,T.N.T. et al. (2021)
	R. norvegicus	(mutant ô°€?4(P195Q)ô°?2)	39 nM	[31-49]		nicotine	Dutertre,S. et al. (2007)

Ki: Nicotinic acetylcholine receptors

Target	Organism	Ki		Competitor	Agonist	Ref
AChBP	L. stagnalis	1.1 nM	+/-0.4	I-Bgt(10 uM)		Dutertre,S. et al. (2007)

References

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

Beissner,M., Dutertre,S., Schemm,R., Danker,T., Sporning,A., Grubmüller,H. and Nicke,A. (2012) Efficient binding of 4/7 α-conotoxins to nicotinic α4β2 receptors is prevented by Arg185 and Pro195 in the α4 subunit Mol. Pharmacol 82:711-718

Ho,T.N.T., Abraham,N., Lewis,R.J. (2021) Rigidity of loop 1 contributes to equipotency of globular and ribbon isomers of α-conotoxin AusIA Sci Rep 11:21928

Lin,B., Xiang,S., and Li,M. (2016) Residues Responsible for the Selectivity of α-Conotoxins for Ac-AChBP or nAChRs. Marine drugs 14:173

Internal links

Nucleic acids
Structure	ACHBP-TARGETED A-CONOTOXIN CORRELATES DISTINCT BINDING ORIENTATIONS WITH NACHR SUBTYPE SELECTIVITY.

External links

Tools