Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
A multidisciplinary strategy for discovery of new Conus venom peptides combines molecular genetics and phylogenetics with peptide chemistry and neuropharmacology. Here we describe application of this approach to the conantokin family of conopeptides targeting NMDA receptors. A new conantokin from Conus rolani, ConRl-A, was identified using molecular phylogeny and subsequently synthesized and functionally characterized. ConRl-A is a 24-residue peptide containing three gamma-carboxyglutamic acid residues with a number of unique sequence features compared to conantokins previously characterized. The HPLC elution of ConRl-A suggested that this peptide exists as two distinct, slowly exchanging conformers. ConRl-A is predominantly helical (estimated helicity of 50%), both in the presence and absence of Ca(++). The order of potency for blocking the four NMDA receptor subtypes by ConRl-A was NR2B > NR2D > NR2A > NR2C. This peptide has a greater discrimination between NR2B and NR2C than any other ligand reported so far. In summary, ConRl-A is a new member of the conantokin family that expands our understanding of structure/function of this group of peptidic ligands targeted to NMDA receptors. Thus, incorporating phylogeny in the discovery of novel ligands for the given family of ion channels or receptors is an efficient means of exploring the megadiverse group of peptides from the genus Conus.
Bandyopadhyay,
Conantokin-G precursor and its role in gamma-carboxylation by a vitamin K-dependent carboxylase from a Conus snail.
1998, Pubmed
Bandyopadhyay,
Conantokin-G precursor and its role in gamma-carboxylation by a vitamin K-dependent carboxylase from a Conus snail.
1998,
Pubmed
Blandl,
NMDA-receptor antagonist requirements in conantokin-G.
1998,
Pubmed
Blandl,
Sequence requirements for the N-methyl-D-aspartate receptor antagonist activity of conantokin-R.
2001,
Pubmed
Bush,
Hydrophobic amino acids define the carboxylation recognition site in the precursor of the gamma-carboxyglutamic-acid-containing conotoxin epsilon-TxIX from the marine cone snail Conus textile.
1999,
Pubmed
Cnudde,
The crystal structures of the calcium-bound con-G and con-T[K7gamma] dimeric peptides demonstrate a metal-dependent helix-forming motif.
2007,
Pubmed
Czerwiec,
Novel gamma-carboxyglutamic acid-containing peptides from the venom of Conus textile.
2006,
Pubmed
Duda,
Molecular genetics of ecological diversification: duplication and rapid evolution of toxin genes of the venomous gastropod Conus.
1999,
Pubmed
Espiritu,
Venomous cone snails: molecular phylogeny and the generation of toxin diversity.
2001,
Pubmed
Gowd,
Conantokin-P, an unusual conantokin with a long disulfide loop.
2008,
Pubmed
Gowd,
Novel peptides of therapeutic promise from Indian Conidae.
2005,
Pubmed
Gray,
Conotoxin MI. Disulfide bonding and conformational states.
1983,
Pubmed
Haack,
Conantokin-T. A gamma-carboxyglutamate containing peptide with N-methyl-d-aspartate antagonist activity.
1990,
Pubmed
Huber,
Identification of amino acids in the gamma-carboxylation recognition site on the propeptide of prothrombin.
1990,
Pubmed
Jacobsen,
The contryphans, a D-tryptophan-containing family of Conus peptides: interconversion between conformers.
1998,
Pubmed
Jacobsen,
A novel D-leucine-containing Conus peptide: diverse conformational dynamics in the contryphan family.
1999,
Pubmed
Jakubowski,
Determining sequences and post-translational modifications of novel conotoxins in Conus victoriae using cDNA sequencing and mass spectrometry.
2004,
Pubmed
Jimenez,
Bromocontryphan: post-translational bromination of tryptophan.
1997,
Pubmed
Jimenez,
Contryphans from Conus textile venom ducts.
2001,
Pubmed
Jimenez,
Conantokin-L, a new NMDA receptor antagonist: determinants for anticonvulsant potency.
2002,
Pubmed
Jimenéz,
Contryphan is a D-tryptophan-containing Conus peptide.
1996,
Pubmed
Larkin,
Clustal W and Clustal X version 2.0.
2007,
Pubmed
Laurie,
Regional and developmental heterogeneity in splicing of the rat brain NMDAR1 mRNA.
1994,
Pubmed
Layer,
Conantokins: peptide antagonists of NMDA receptors.
2004,
Pubmed
Lirazan,
The spasmodic peptide defines a new conotoxin superfamily.
2000,
Pubmed
Massilia,
Contryphan-Vn: a novel peptide from the venom of the Mediterranean snail Conus ventricosus.
2001,
Pubmed
Mena,
Conantokin-G: a novel peptide antagonist to the N-methyl-D-aspartic acid (NMDA) receptor.
1990,
Pubmed
Nam,
Multiple genes elucidate the evolution of venomous snail-hunting Conus species.
2009,
Pubmed
O'Neal,
Multiple cis-trans conformers of the prolactin receptor proline-rich motif (PRM) peptide detected by reverse-phase HPLC, CD and NMR spectroscopy.
1996,
Pubmed
Olivera,
Conus peptides: biodiversity-based discovery and exogenomics.
2006,
Pubmed
Olivera,
Diversity of the neurotoxic Conus peptides: a model for concerted pharmacological discovery.
2007,
Pubmed
Olivera,
Subtype-selective conopeptides targeted to nicotinic receptors: Concerted discovery and biomedical applications.
2008,
Pubmed
Olivera,
Speciation of cone snails and interspecific hyperdivergence of their venom peptides. Potential evolutionary significance of introns.
1999,
Pubmed
Pallaghy,
Solution structure of contryphan-R, a naturally occurring disulfide-bridged octapeptide containing D-tryptophan: comparison with protein loops.
1999,
Pubmed
Prorok,
Structure-function relationships of the NMDA receptor antagonist conantokin peptides.
2001,
Pubmed
Rigby,
A conotoxin from Conus textile with unusual posttranslational modifications reduces presynaptic Ca2+ influx.
1999,
Pubmed
Shi,
A striking periodicity of the cis/trans isomerization of proline imide bonds in cyclic disulfide-bridged peptides.
2006,
Pubmed
Teichert,
Novel conantokins from Conus parius venom are specific antagonists of N-methyl-D-aspartate receptors.
2007,
Pubmed
Trabelsi,
Study of the cis-trans isomerization of enalapril by reversed-phase liquid chromatography.
2000,
Pubmed
Twede,
Neuroprotective and cardioprotective conopeptides: an emerging class of drug leads.
2009,
Pubmed
Twede,
Conantokin-Br from Conus brettinghami and selectivity determinants for the NR2D subunit of the NMDA receptor.
2009,
Pubmed
,
Xenbase
Walker,
The T-superfamily of conotoxins.
1999,
Pubmed
Warder,
Amino acid determinants for NMDA receptor inhibition by conantokin-T.
2001,
Pubmed
White,
In vitro and in vivo characterization of conantokin-R, a selective NMDA receptor antagonist isolated from the venom of the fish-hunting snail Conus radiatus.
2000,
Pubmed
,
Xenbase