PROSITE documentation PDOC60025

Conantokin family signature




Description

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.

Expert(s) to contact by email:

Ramakumar S.

Last update:

January 2006 / First entry.

Technical section

PROSITE method (with tools and information) covered by this documentation:

CONANTOKIN, PS60025; Conantokin family signature  (PATTERN)


References

1AuthorsRigby A.C., Baleja J.D., Li L., Pedersen L.G., Furie B.C., Furie B.
TitleRole of gamma-carboxyglutamic acid in the calcium-induced structural transition of conantokin G, a conotoxin from the marine snail Conus geographus.
SourceBiochemistry 36:15677-15684(1997).
PubMed ID9398296
DOI10.1021/bi9718550

2AuthorsBandyopadhyay P.K., Colledge C.J., Walker C.S., Zhou L.-M., Hillyard D.R., Olivera B.M.
TitleConantokin-G precursor and its role in gamma-carboxylation by a vitamin K-dependent carboxylase from a Conus snail.
SourceJ. Biol. Chem. 273:5447-5450(1998).
PubMed ID9488665

3AuthorsProrok M., Castellino F.J.
TitleStructure-function relationships of the NMDA receptor antagonist conantokin peptides.
SourceCurr. Drug. Targets. 2:313-322(2001).
PubMed ID11554555

4AuthorsBlandl T., Zajicek J., Prorok M., Castellino F.J.
TitleSequence requirements for the N-methyl-D-aspartate receptor antagonist activity of conantokin-R.
SourceJ. Biol. Chem. 276:7391-7396(2001).
PubMed ID11096077
DOI10.1074/jbc.M006648200

5AuthorsJimenez E.C., Donevan S., Walker C., Zhou L.-M., Nielsen J., Cruz L.J., Armstrong H., White H.S., Olivera B.M.
TitleConantokin-L, a new NMDA receptor antagonist: determinants for anticonvulsant potency.
SourceEpilepsy. Res. 51:73-80(2002).
PubMed ID12350383



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