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

Journal Article · Tue Aug 23 04:00:00 EDT 1988 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00417a009· OSTI ID:6464923

Yanagawa, Y; Abe, T; Satake, M; Odani, S; Suzuki, J; Ishikawa, K

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.

• Research Organization: Niigata Univ. (Japan)
• OSTI ID: 6464923
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 27:17; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACID SEQUENCE
ANIMALS
ANTIGENS
AQUATIC ORGANISMS
BIOCHEMICAL REACTION KINETICS
CHEMICAL REACTIONS
CHROMATOGRAPHY
CROSS-LINKING
INVERTEBRATES
KINETICS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
MATERIALS
MEMBRANE TRANSPORT
MOLECULAR STRUCTURE
MOLLUSCS
MUSCLES
POLYMERIZATION
REACTION KINETICS
SEPARATION PROCESSES
SNAILS
TOXIC MATERIALS
TOXINS
TRITIUM COMPOUNDS