PROSITE documentation PDOC60025 [for PROSITE entry PS60025]

Conantokin family signature

The conantokins are a family of neuroactive peptides found in the venoms of fish-hunting cone snails. They possess a high content of γ-carboxyglutamic acid (Gla) (4-5 residues), a non-standard amino-acid made by the post-translational modification of glutamate (Glu) residue. Conantokins are the only natural biochemical-characterized peptides known to be N-methyl-D-aspartate (NMDA) receptor antagonists. They are one class of agents that show therapeutic promise in treating conditions associated with NMDA receptor dysfunction. In animal models they have exhibited anticonvulsant and anti-Parkinsonian properties and have provided neuroprotection within therapeutically acceptable times following transient focal brain ischemia [1,2,3,4,5].

Upon binding of Ca2+ to Gla, conantokin undergoes a conformational transition from a distorted curvilinear 3(10) helix to a linear α-helix (see <PDV:1AD7> and <PDB:1AWY>). The binding of Ca2+ to conantokin leads to the exposure of a hydrophobic region on the opposite face of the helix [1]. Shared sequence elements of conantokins are relatively few and include sequence identity at the first four residues, homologous positioning of the two most C-terminal Gla residues, and an Arg preceding the most C-terminal Gla [3].

The conantokin family is currently known to include:

• Conotoxin G from Conus geographus (Geography cone) (Nubecula geographus).
• Conantokin-L from Conus lynceus (Lynceus cone).
• Conantokin-R from Conus radiatus (Rayed cone).
• Conantokin-T from Conus tulipa (Fish-hunting cone snail) (Tulip cone).

The pattern we developed for the conantokin family covers the Gla residues.