BuIA (P00026) Protein Card

General Information

Name	BuIA
Alternative name(s)	Bu1a
Organism	Conus bullatus
Organism region	Indo-Pacific
Organism diet	piscivorous
Protein Type	Wild type
Protein precursor	BuIA precursor (409)

Classification

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

Sequence

GCCSTPPCAVLYC(nh2)

Modified residues

position	symbol	name
14	nh2	C-term amidation

Sequence evidence

nucleic acid level

Average Mass

1311.56

Monoisotopic Mass

1310.49

Isoelectric Point

8.09

Extinction Coefficient [280nm]

1490.00

Activity

IC50: Nicotinic acetylcholine receptors

Target	Organism	IC50		n_hill	Agonist	Ref
α2β2	R. norvegicus	800nM		0.85	100uM Ach	Azam,L. et al. (2005)
α2β4	R. norvegicus	121nM		1.31	100uM Ach	Azam,L. et al. (2005)
α3β2	H. sapiens	7.8 nM	+/-0.4		100 uM Ach	Wei,N. et al. (2021)
	R. norvegicus	5.72nM		1.48	100uM Ach	Azam,L. et al. (2005)
α3β4	R. norvegicus	27.7nM		1.52	100uM Ach	Azam,L. et al. (2005)
α4β2	R. norvegicus	10.4uM		0.525	100uM Ach	Azam,L. et al. (2005)
α4β4	R. norvegicus	69.9nM		1.15	100uM Ach	Azam,L. et al. (2005)
α6/α3β2	R. norvegicus	258pM		0.963	100uM Ach	Azam,L. et al. (2005)
α6/α3β2β3	R. norvegicus	460pM	+/-150	1.3	100uM Ach	Azam,L. et al. (2010)
α6/α3β4	R. norvegicus	1.54nM		1.4	100uM Ach	Azam,L. et al. (2005)
		2.1nM	+/-0.4	1.7	100uM Ach	Azam,L. et al. (2010)
α7	R. norvegicus	272nM		1.21	100uM Ach	Azam,L. et al. (2005)

Kd: Nicotinic acetylcholine receptors

Target	Organism	Kd	Ref
α2β4	R. norvegicus	62.9nM	Azam,L. et al. (2005)
α3β2	R. norvegicus	5.85nM	Shiembob,D.L. et al. (2006)
α3β4	R. norvegicus	23.8nM	Azam,L. et al. (2005)
α4β4	R. norvegicus	21.8nM	Azam,L. et al. (2005)
α6/α3β4	R. norvegicus	2.58nM	Azam,L. et al. (2005)

Ki: Nicotinic acetylcholine receptors

Target	Organism	Ki		Competitor	Agonist	Ref
α7	R. norvegicus	19.7 nM	+/-2.85			Liu et al. (2019)

Synthetic variants

BuIA[A9S]	GCCSTPPCSVLYC(nh2)
BuIA[C2H,C8F]	GHCSTPPFAVLYC(nh2)
BuIA[C2S,C8S]	GSCSTPPSAVLYC
BuIA[C3S,del9-13]	GCSSTPPC
BuIA[G1K,del2,C8S]	KCSTPPDAVLYC
BuIA[L11A]	GCCSTPPCAVAYC(nh2)
BuIA[P6O]	GCCSTOPCAVLYC(nh2)
BuIA[P7O]	GCCSTPOCAVLYC(nh2)
BuIA[S4A]	GCCATPPCAVLYC(nh2)
BuIA[T5A,P6O]	GCCSAOPCAVLYCG(nh2)
BuIA[T5A]	GCCSAPPCAVLYC(nh2)
BuIA[V10A]	GCCSTPPCAALYC(nh2)
BuIA[Y12A]	GCCSTPPCAVLAC(nh2)
BuIA[Y12F]	GCCSTPPCAVLFC(nh2)

References

Chi,S.W., Kim,D.H., Olivera,B.M., McIntosh,J.M. and Han,K.H. (2006) NMR structure determination of alpha-conotoxin BuIA, a novel neuronal nicotinic acetylcholine receptor antagonist with an unusual 4/4 disulfide scaffold Biochem. Biophys. Res. Commun. 349:1228-1234

Azam,L., Dowell,C., Watkins,M., Stitzel,J.A., Olivera,B.M. and McIntosh,J.M. (2005) Alpha-conotoxin BuIA, a novel peptide from Conus bullatus, distinguishes among neuronal nicotinic acetylcholine receptors J. Biol. Chem. 280:80-87

Jin,A.H., Brandstaetter,H., Nevin,S.T., Tan,C.C., Clark,R.J., Adams,D.J., Alewood,P.F., Craik,D.J. and Daly,N.L. (2007) Structure of alpha-conotoxin BuIA: influences of disulfide connectivity on structural dynamics. BMC Struct. Biol. 7:28

Shiembob,D.L., Roberts,R.L., Luetje,C.W. and McIntosh,J.M. (2006) Determinants of alpha-conotoxin BuIA selectivity on the nicotinic acetylcholine receptor beta subunit. Biochemistry 45:11200-11207

Liu, C., Wu, P., Zhu, H., Grieco, P., Yu, R., Gao, X., Wu, G., Wang, D., Xu, H. and Qi, W. (2019) Rationally Designed α-Conotoxin Analogues Maintained Analgesia Activity and Weakened Side Effects Molecules 24:337

Tabassum, N., Tae, H.S., Jia, X., Kaas, Q., Jiang, T., Adams, D.J. and Yu, R. (2017) Role of CysI-CysIII Disulfide Bond on the Structure and Activity of α-Conotoxins at Human Neuronal Nicotinic Acetylcholine Receptors ACS omega 2:4621-4631

Wei,N., Chu,Y., Liu,H., Xu,Q. and Yu,R. (2021) Antagonistic Mechanism of α-Conotoxin BuIA toward the Human α3β2 Nicotinic Acetylcholine Receptor. ACS Chem Neurosci 12:4535-4545

Internal links

Protein Precursor	BuIA precursor (409)
Nucleic acids
Structure	SOLUTION STRUCTURE OF ALPHA-CONOTOXIN BUIA SOLUTION STRUCTURE OF RIBBON BUIA Crystal structure of acetylcholine binding protein (AChBP) from Aplysia Californica in complex with alpha-conotoxin BuIA

External links

Ncbi

2I28_A, 4EZ1_K, 4EZ1_L, 4EZ1_N, 4EZ1_O

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