title: Conantokin-T. A gamma-carboxyglutamate containing peptide with N-methyl-d-aspartate antagonist activity.
abstract: Conantokin-T, a 21-amino acid peptide which induces sleep-like symptoms in young mice was purified from the venom of the fish-hunting cone snail, Conus tulipa. The amino acid sequence of the peptide was determined and verified by chemical synthesis. The peptide has 4 residues of the modified amino acid, gamma-carboxyglutamate (Gla). The sequence of the peptide is: Gly-Glu-Gla-Gla-Tyr-Gln-Lys-Met-Leu-Gla-Asn-Leu-Arg-Gla-Ala-Glu-Val-Lys- Lys-Asn-Ala-NH2. Conantokin-T inhibits N-methyl-D-aspartate (NMDA) receptor-mediated calcium influx in central nervous system neurons. This observation suggests that like conantokin-G (a homologous Conus peptide with recently identified NMDA antagonist activity) conantokin-T has NMDA antagonist activity. A sequence comparison of conantokins-T and -G identifies the 4 Gla residues and the N-terminal dipeptide sequence as potential key elements for the biological activity of this peptide.
authors.affiliation: Department of Biology, University of Utah, Salt Lake City 84112.
authors.forename: J A
authors.initials: JA
authors.lastname: Haack
authors.forename: J
authors.initials: J
authors.lastname: Rivier
authors.forename: T N
authors.initials: TN
authors.lastname: Parks
authors.forename: E E
authors.initials: EE
authors.lastname: Mena
authors.forename: L J
authors.initials: LJ
authors.lastname: Cruz
authors.forename: B M
authors.initials: BM
authors.lastname: Olivera
mesh_terms: D015055:1-Carboxyglutamic Acid / Q000032:analysis*; D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002850:Chromatography, Gel; D020916:Conotoxins; D005456:Fluorescent Dyes; D016257:Fura-2; D036341:Intercellular Signaling Peptides and Proteins; D013058:Mass Spectrometry; D051379:Mice; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D016202:N-Methylaspartate; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D051381:Rats; D012640:Seizures / Q000139:chemically induced; D012689:Sequence Homology, Nucleic Acid; D012908:Snails
chemical_list: D001572:Benzofurans; D020916:Conotoxins; D005456:Fluorescent Dyes; D036341:Intercellular Signaling Peptides and Proteins; D008978:Mollusk Venoms; D010455:Peptides; C063571:conantokin-T; D001224:Aspartic Acid; D015055:1-Carboxyglutamic Acid; D016202:N-Methylaspartate; D002118:Calcium; D016257:Fura-2