{PDOC60025}
{PS60025; CONANTOKIN}
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* Conantokin family signature *
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The conantokins  are  a  family of neuroactive peptides found in the venoms of
fish-hunting cone snails. They possess a high content of gamma-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 to 5].

Upon binding  of Ca2+ to Gla, conantokin undergoes a conformational transition
from a  distorted  curvilinear  3(10)  helix  to  a  linear  alpha-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.

-Conserved pattern: G-E-E-E-x(2)-[KE]-{E}(2)-x(0,1)-E-x-[ILA]-R-E
                    [The 4-5 last E's are gamma-carboxylated]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Expert(s) to contact by email:
           Ramakumar S.; ramak@physics.iisc.ernet.in

-Last update: January 2006 / First entry.

[ 1] Rigby A.C., Baleja J.D., Li L., Pedersen L.G., Furie B.C., Furie B.
     "Role of gamma-carboxyglutamic acid in the calcium-induced structural
     transition of conantokin G, a conotoxin from the marine snail Conus
     geographus."
     Biochemistry 36:15677-15684(1997).
     PubMed=9398296; DOI=10.1021/bi9718550
[ 2] Bandyopadhyay P.K., Colledge C.J., Walker C.S., Zhou L.-M.,
     Hillyard D.R., Olivera B.M.
     "Conantokin-G precursor and its role in gamma-carboxylation by a
     vitamin K-dependent carboxylase from a Conus snail."
     J. Biol. Chem. 273:5447-5450(1998).
     PubMed=9488665
[ 3] Prorok M., Castellino F.J.
     "Structure-function relationships of the NMDA receptor antagonist
     conantokin peptides."
     Curr. Drug. Targets. 2:313-322(2001).
     PubMed=11554555
[ 4] Blandl T., Zajicek J., Prorok M., Castellino F.J.
     "Sequence requirements for the N-methyl-D-aspartate receptor
     antagonist activity of conantokin-R."
     J. Biol. Chem. 276:7391-7396(2001).
     PubMed=11096077; DOI=10.1074/jbc.M006648200
[ 5] Jimenez E.C., Donevan S., Walker C., Zhou L.-M., Nielsen J., Cruz L.J.,
     Armstrong H., White H.S., Olivera B.M.
     "Conantokin-L, a new NMDA receptor antagonist: determinants for
     anticonvulsant potency."
     Epilepsy. Res. 51:73-80(2002).
     PubMed=12350383

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