|PROSITE documentation PDOC60025|
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 . 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 .
The conantokin family is currently known to include:
The pattern we developed for the conantokin family covers the Gla residues.Expert(s) to contact by email:
January 2006 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Rigby A.C., Baleja J.D., Li L., Pedersen L.G., Furie B.C., Furie B.|
|Title||Role of gamma-carboxyglutamic acid in the calcium-induced structural transition of conantokin G, a conotoxin from the marine snail Conus geographus.|
|2||Authors||Bandyopadhyay P.K., Colledge C.J., Walker C.S., Zhou L.-M., Hillyard D.R., Olivera B.M.|
|Title||Conantokin-G precursor and its role in gamma-carboxylation by a vitamin K-dependent carboxylase from a Conus snail.|
|Source||J. Biol. Chem. 273:5447-5450(1998).|
|3||Authors||Prorok M., Castellino F.J.|
|Title||Structure-function relationships of the NMDA receptor antagonist conantokin peptides.|
|Source||Curr. Drug. Targets. 2:313-322(2001).|
|4||Authors||Blandl T., Zajicek J., Prorok M., Castellino F.J.|
|Title||Sequence requirements for the N-methyl-D-aspartate receptor antagonist activity of conantokin-R.|
|Source||J. Biol. Chem. 276:7391-7396(2001).|
|5||Authors||Jimenez E.C., Donevan S., Walker C., Zhou L.-M., Nielsen J., Cruz L.J., Armstrong H., White H.S., Olivera B.M.|
|Title||Conantokin-L, a new NMDA receptor antagonist: determinants for anticonvulsant potency.|
|Source||Epilepsy. Res. 51:73-80(2002).|