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

Journal Article · Tue Aug 23 00:00:00 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), Vol. 27:17
• Country of Publication: United States
• Language: English

Related Subjects

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