LvIA (P05949) Protein Card

General Information
Name LvIA
Organism Conus lividus
Organism region Indo-Pacific
Organism diet vermivorous
Protein Type Wild type
Protein precursor LvIA precursor (5886)
Notes

Zhu, X et al., 2016 reported recombinantly-expressed LvIA used in a hot-plate pain model produced increased latency which was maximal 90 min after treatment (24.17 s reaction time).

Kondasinghe,T.D et al.,2019 reported three on-resin strategies to efficiently synthesize LvIA.


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

Sequence
GCCSHPACNVDHPEIC(nh2)
Modified residues
positionsymbolname
17nh2C-term amidation
Sequence evidence nucleic acid level
Average Mass 1679.87
Monoisotopic Mass 1678.61
Isoelectric Point 5.63
Extinction Coefficient [280nm] -1.00

Activity

IC50: Nicotinic acetylcholine receptors

TargetOrganismIC50nhillCompetitorAgonistRef
α3β2H. sapiens(Recombinant peptide against Xenopus oocyte expressing human nAChR subtype.)46.8 nMACh (100 uM)Zhu,X. et al. (2016)
R. norvegicus(Recombinant peptide against Xenopus oocyte expressing rat nAChR subtype.)160.8 nMACh (100 uM)Zhu,X. et al. (2016)
15.6 nM[12.8-19.1]0.71Zhu,X. et al. (2020)
α3β4R. norvegicus283 nM[237-338]1.47Zhu,X. et al. (2020)
AChBPA. californica2300 nM+/-200α-bungarotoxin (0.9 nM)Zhu,X. et al. (2020)

Synthetic variants
LvIA[D11A]GCCSHPACNVAHPEIC(nh2)
LvIA[E14A]GCCSHPACNVDHPAIC(nh2)
LvIA[G1A]ACCSHPACNVDHPEIC(nh2)
LvIA[H12A]GCCSHPACNVDAPEIC(nh2)
LvIA[H5A]GCCSAPACNVDHPEIC(nh2)
LvIA[I15A]GCCSHPACNVDHPEAC(nh2)
LvIA[N9A]GCCSHPACAVDHPEIC(nh2)
LvIA[N9D]GCCSHPACDVDHPEIC(nh2)
LvIA[N9G]GCCSHPACGVDHPEIC(nh2)
LvIA[N9I]GCCSHPACIVDHPEIC(nh2)
LvIA[N9K]GCCSHPACKVDHPEIC(nh2)
LvIA[N9L]GCCSHPACLVDHPEIC(nh2)
LvIA[P13A]GCCSHPACNVDHAEIC(nh2)
LvIA[P6A]GCCSHAACNVDHPEIC(nh2)
LvIA[S4A]GCCAHPACNVDHPEIC(nh2)
LvIA[V10A]GCCSHPACNADHPEIC(nh2)

References
Luo,S., Zhangsun,D., Schroeder,C.I., Zhu,X., Hu,Y., Wu,Y., Weltzin,M.M., Eberhard,S., Kaas,Q., Craik,D.J., McIntosh,J.M. and Whiteaker,P. (2014) A novel α4/7-conotoxin LvIA from Conus lividus that selectively blocks α3β2 vs. α6/α3β2β3 nicotinic acetylcholine receptors. FASEB J. 28:1842-1853
Zhu,X., Bi,J., Yu,J., Li,X., Zhang,Y., Zhangsun,D. and Luo,S. (2016) Recombinant Expression and Characterization of α-Conotoxin LvIA in Escherichia coli. Mar Drugs 14
Kondasinghe, T.D., Saraha, H.Y., Jackowski, S.T. and Stockdill, J.L. (2019) Raising the bar on-bead: Efficient on-resin synthesis of α-conotoxin LvIA Tetrahedron letters 60:23-28
Zhu,X., Pan,S., Xu,M., Zhang,L., Yu,J., Yu,J., Wu,Y., Fan,Y., Li,H., Kasheverov,I.E., Kudryavtsev,D.S., Tsetlin,V.I., Xue,Y., Zhangsun,D., Wang,X. and Luo,S. (2020) High Selectivity of an α-Conotoxin LvIA Analogue for α3β2 Nicotinic Acetylcholine Receptors Is Mediated by β2 Functionally Important Residues. J Med Chem 63:13656-13668

Internal links
Protein Precursor LvIA precursor (5886)
Nucleic acids
Structure A novel α4/7-conotoxin LvIA from Conus lividus that selectively blocks α3β2 vs. α6/α3β2β3 nicotinic acetylcholine receptors
Co-crystal structure of Ac-AChBPP in complex with alpha-conotoxin LvIA

External links
Ncbi 2MDQ_A

Tools