title: A novel arrangement of Cys residues in a paralytic peptide of Conus cancellatus (jr. syn.: Conus austini), a worm-hunting snail from the Gulf of Mexico.
abstract: The present study details the purification, the amino acid sequence determination, and a preliminary characterization of the biological effects in mice of a new conotoxin from the venom of Conus cancellatus (jr. syn.: Conus austini), a worm-hunting cone snail collected in the western Gulf of Mexico (Mexico). The 23-amino acid peptide, called as25a, is characterized by the sequence pattern CX1CX2CX8CX1CCX5, which is, for conotoxins, a new arrangement of six cysteines (framework XXV) that form three disulfide bridges. The primary structure (CKCPSCNFNDVTENCKCCIFRQP*; *, amidated C-terminus; calculated monoisotopic mass, 2644.09Da) was established by automated Edman degradation after reduction and alkylation, and MALDI-TOF and ESI mass spectrometry (monoisotopic mass, 2644.12/2644.08Da). Upon intracranial injection in mice, the purified peptide provokes paralysis of the hind limbs and death with a dose of 240 pmol (~0.635 μg, ~24.9 ng/g). In addition, a post-translational variant of this peptide (as25b) was identified and determined to contain two hydroxyproline residues. These peptides may represent a novel conotoxin gene superfamily.
authors.affiliation: Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro 76230, Mexico. maguilar@unam.mx
authors.forename: Manuel B
authors.initials: MB
authors.lastname: Aguilar
authors.forename: Alejandro
authors.initials: A
authors.lastname: Zugasti-Cruz
authors.forename: Andrés
authors.initials: A
authors.lastname: Falcón
authors.forename: César V F
authors.initials: CV
authors.lastname: Batista
authors.forename: Baldomero M
authors.initials: BM
authors.lastname: Olivera
authors.forename: Edgar P Heimer
authors.initials: EP
authors.lastname: de la Cotera
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D020916:Conotoxins / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D052078:Conus Snail; D003545:Cysteine / Q000737:chemistry*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry / Q000633:toxicity; D010264:Paraplegia / Q000139:chemically induced; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid
chemical_list: D020916:Conotoxins; D009479:Neuropeptides; D003545:Cysteine