7LQR

Structure of conotoxin CIC

Summary for 7LQR

• Entry DOI: 10.2210/pdb7lqr/pdb
• Descriptor: Alpha-conotoxin CIC (1 entity in total)
• Functional Keywords: nicotinic acetylcholine receptor antagonist, toxin
• Biological source: Conus catus (Cat cone)
• Total number of polymer chains: 1
• Total formula weight: 2111.30

Authors

Evans, E.R.J.,Daly, N.L. (deposition date: 2021-02-15, release date: 2021-04-21, Last modification date: 2024-10-30)

Primary citation

Giribaldi, J.,Haufe, Y.,Evans, E.R.J.,Wilson, D.T.,Daly, N.L.,Enjalbal, C.,Nicke, A.,Dutertre, S.
Synthesis, Structural and Pharmacological Characterizations of CIC, a Novel alpha-Conotoxin with an Extended N-Terminal Tail.
Mar Drugs, 19:-, 2021

PubMed Abstract: Cone snails are venomous marine predators that rely on fast-acting venom to subdue their prey and defend against aggressors. The conotoxins produced in the venom gland are small disulfide-rich peptides with high affinity and selectivity for their pharmacological targets. A dominant group comprises α-conotoxins, targeting nicotinic acetylcholine receptors. Here, we report on the synthesis, structure determination and biological activity of a novel α-conotoxin, CIC, found in the predatory venom of the piscivorous species and its truncated mutant Δ-CIC. CIC is a 4/7 α-conotoxin with an unusual extended N-terminal tail. High-resolution NMR spectroscopy shows a major influence of the N-terminal tail on the apparent rigidity of the three-dimensional structure of CIC compared to the more flexible Δ-CIC. Surprisingly, this effect on the structure does not alter the biological activity, since both peptides selectively inhibit α3β2 and α6/α3β2β3 nAChRs with almost identical sub- to low micromolar inhibition constants. Our results suggest that the N-terminal part of α-conotoxins can accommodate chemical modifications without affecting their pharmacology.

PubMed: 33801301
DOI: 10.3390/md19030141

Experimental method

SOLUTION NMR