RgIA [C3(Smc),S4T,Y10(Ity),R11Q,ins13(bhY)] (P10458) Protein Card

General Information

Name	RgIA [C3(Smc),S4T,Y10(Ity),R11Q,ins13(bhY)] (named by ConoServer)
Alternative name(s)	RgIA-5524
Organism	synthetic construct
Protein Type	Synthetic
Parent	RgIA
Notes	According to Zheng et al.(2021), RgIA-5524:(i) has a methylene thioacetal bond formed between (Smc)3 and C12; (ii) exhibits highly selective inhibition of α9α10 nAChRs and significantly improved stability; (iii) relieves chemotherapy-induced neuropathic pain in wild type mouse model; (iv) has no significant effect on α9 knockout mouse model which indicates the requirement of α9-containing nAChRs for the therapeutic effects.

Classification

Conopeptide class	conotoxin
Gene superfamily
Pharmacological family	alpha conotoxin

Sequence

GC(Smc)TDPRCR(Ity)QC(bhY)R
Modified residues	position symbol name 3 Smc S-Methylcystine 10 Ity 3-iodotyrosine 13 bhY L-β-homotyrosine
Average Mass	1874.90
Monoisotopic Mass	1873.59
Isoelectric Point	12.20
Extinction Coefficient [280nm]	125.00

Activity

IC50: Nicotinic acetylcholine receptors

Target	Organism	IC50		Agonist	Ref
α2β2	H. sapiens	>10000 nM		100 uM ACh	Zheng N et al. (2021)
α2β4	H. sapiens	>10000 nM		100 uM ACh	Zheng N et al. (2021)
α3β2	H. sapiens	>10000 nM		100 uM ACh	Zheng N et al. (2021)
α3β4	H. sapiens	>10000 nM		100 uM ACh	Zheng N et al. (2021)
α4β2	H. sapiens	>10000 nM		100 uM ACh	Zheng N et al. (2021)
α4β4	H. sapiens	>10000 nM		100 uM ACh	Zheng N et al. (2021)
α6/α3β2β3	H. sapiens	>10000 nM		100 uM ACh	Zheng N et al. (2021)
α6/α3β4	H. sapiens	>10000 nM		100 uM ACh	Zheng N et al. (2021)
α7	H. sapiens	186 nM		200 uM ACh	Zheng N et al. (2021)
α9α10	H. sapiens	0.9 nM	[0.8-1.1]	100 uM ACh	Zheng N et al. (2021)

References

Zheng N, Christensen SB, Dowell C, Purushottam L, Skalicky JJ, McIntosh JM, Chou DH. (2021) Discovery of Methylene Thioacetal-Incorporated α-RgIA Analogues as Potent and Stable Antagonists of the Human α9β10 Nicotinic Acetylcholine Receptor for the Treatment of Neuropathic Pain J Med Chem 64:9513-9524

Internal links

Nucleic acids
Structure

External links

Tools

Please cite:
Kaas Q, Yu R, Jin AH, Dutertre S and Craik DJ. ConoServer: updated content, knowledge, and discovery tools in the conopeptide database. Nucleic Acids Research (2012) 40(Database issue):D325-30
Kaas Q, Westermann JC, Halai R, Wang CK and Craik DJ. ConoServer, a database for conopeptide sequences and structures. Bioinformatics (2008) 24(3):445-6

ConoServer is managed at the Institute of Molecular Bioscience IMB, Brisbane, Australia.

The database and computational tools found on this website may be used for academic research only, provided that it is referred to ConoServer, the database of conotoxins (http://www.conoserver.org) and the above reference is cited. For any other use please contact David Craik (d.craik@imb.uq.edu.au).

Contacts:
David Craik
Quentin Kaas

Last updated: Sunday 28 May 2023