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Title: Novel sodium channel inhibitor from Conus geographus: purification, structure, and pharmacological properties

Abstract

A novel toxin, tentatively named conotoxin GS (CGS), has been isolated form a marine snail, Conus geographus. CGS was found to exist as a single polypeptide chain, consisting of 34 amino acid residues, cross-linked by three disulfide bonds. Its amino acid sequence was shown to be Ala-Cys-Ser-Gly-Arg-Gly-Ser-Arg-Cys-Hyp-Hyp-Gln-Cys-Cys-Met-Gly-Leu-Arg-Cys-Gly-Arg-Gly-Asn-Pro-Gln-Lys-Cys-Ile-Gly-Ala-His-Gla-Asp-Val. In competition experiments, CGS inhibited the bindings of (/sup 3/H)Lys-tetrodotoxin ((/sup 3/H)Lys-TTX) and (/sup 3/H)propionylconotoxin GIIIA to Electrophorus electricus electroplax membranes, with K/sub i/ values of 34 nM and 24 nM, respectively. The toxin inhibited the binding of (/sup 3/H)Lys-TTX (1 nM) to rat skeletal muscle homogenates with an IC/sub 50/ value of 880 nM but showed very little effect on this binding to the rat brain P/sub 2/ fraction at 10 ..mu..M. These binding studies indicate that CGS belongs to the same group of Na channel inhibitors as TTX, STX (saxitoxin), and ..mu..-conotoxins. Although CGS, like the ..mu..-conotoxins, is a pharmacological probe for distinguishing between neuronal and muscle Na channel subtypes, the homology in the sequences of CGS and ..mu..-conotoxins is very limited.

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Niigata Univ. (Japan)
OSTI Identifier:
6464923
Resource Type:
Journal Article
Journal Name:
Biochemistry; (United States)
Additional Journal Information:
Journal Volume: 27:17
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; MEMBRANE TRANSPORT; BIOCHEMICAL REACTION KINETICS; TOXINS; AMINO ACID SEQUENCE; CROSS-LINKING; LIQUID COLUMN CHROMATOGRAPHY; MUSCLES; SNAILS; TRITIUM COMPOUNDS; ANIMALS; ANTIGENS; AQUATIC ORGANISMS; CHEMICAL REACTIONS; CHROMATOGRAPHY; INVERTEBRATES; KINETICS; LABELLED COMPOUNDS; MATERIALS; MOLECULAR STRUCTURE; MOLLUSCS; POLYMERIZATION; REACTION KINETICS; SEPARATION PROCESSES; TOXIC MATERIALS; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Yanagawa, Y, Abe, T, Satake, M, Odani, S, Suzuki, J, and Ishikawa, K. Novel sodium channel inhibitor from Conus geographus: purification, structure, and pharmacological properties. United States: N. p., 1988. Web. doi:10.1021/bi00417a009.
Yanagawa, Y, Abe, T, Satake, M, Odani, S, Suzuki, J, & Ishikawa, K. Novel sodium channel inhibitor from Conus geographus: purification, structure, and pharmacological properties. United States. https://doi.org/10.1021/bi00417a009
Yanagawa, Y, Abe, T, Satake, M, Odani, S, Suzuki, J, and Ishikawa, K. 1988. "Novel sodium channel inhibitor from Conus geographus: purification, structure, and pharmacological properties". United States. https://doi.org/10.1021/bi00417a009.
@article{osti_6464923,
title = {Novel sodium channel inhibitor from Conus geographus: purification, structure, and pharmacological properties},
author = {Yanagawa, Y and Abe, T and Satake, M and Odani, S and Suzuki, J and Ishikawa, K},
abstractNote = {A novel toxin, tentatively named conotoxin GS (CGS), has been isolated form a marine snail, Conus geographus. CGS was found to exist as a single polypeptide chain, consisting of 34 amino acid residues, cross-linked by three disulfide bonds. Its amino acid sequence was shown to be Ala-Cys-Ser-Gly-Arg-Gly-Ser-Arg-Cys-Hyp-Hyp-Gln-Cys-Cys-Met-Gly-Leu-Arg-Cys-Gly-Arg-Gly-Asn-Pro-Gln-Lys-Cys-Ile-Gly-Ala-His-Gla-Asp-Val. In competition experiments, CGS inhibited the bindings of (/sup 3/H)Lys-tetrodotoxin ((/sup 3/H)Lys-TTX) and (/sup 3/H)propionylconotoxin GIIIA to Electrophorus electricus electroplax membranes, with K/sub i/ values of 34 nM and 24 nM, respectively. The toxin inhibited the binding of (/sup 3/H)Lys-TTX (1 nM) to rat skeletal muscle homogenates with an IC/sub 50/ value of 880 nM but showed very little effect on this binding to the rat brain P/sub 2/ fraction at 10 ..mu..M. These binding studies indicate that CGS belongs to the same group of Na channel inhibitors as TTX, STX (saxitoxin), and ..mu..-conotoxins. Although CGS, like the ..mu..-conotoxins, is a pharmacological probe for distinguishing between neuronal and muscle Na channel subtypes, the homology in the sequences of CGS and ..mu..-conotoxins is very limited.},
doi = {10.1021/bi00417a009},
url = {https://www.osti.gov/biblio/6464923}, journal = {Biochemistry; (United States)},
number = ,
volume = 27:17,
place = {United States},
year = {Tue Aug 23 00:00:00 EDT 1988},
month = {Tue Aug 23 00:00:00 EDT 1988}
}