Modification of arginine in sea anemone toxin RTX-III from Radianthus macrodactylus

• Published in: Toxicon (Oxford) Vol. 27; no. 10; p. 1075
• Main Authors: Mahnir, V M, Kozlovskaya, E P, Elyakov, G B
• Format: Journal Article
• Language: English
• Published: England 1989
• Subjects: Aldehydes; Amino Acid Sequence; Animals; Arginine; Chemical Phenomena; Chemistry; Cnidarian Venoms - toxicity; Cyclohexanones; Mice; Molecular Sequence Data; Neurotoxins - toxicity; Pentanones; Phenylglyoxal; Sea Anemones - analysis; Spectrum Analysis; Structure-Activity Relationship
• ISSN: 0041-0101
• DOI: 10.1016/0041-0101(89)90001-9

Chemical modifications of the polypeptide neurotoxin RTX-III have allowed us to study the functional role of Arg residues. The effect of chemical modification has been estimated by measuring toxicity in mice. 2,4-Pentanedione did not react with Arg residues of RTX-III even after 100 hr incubation. Malonic aldehyde reacted readily with RTX-III, yielding an unusual derivative; a Schiff's base obtained by condensation of one of two aldehyde groups of malonic aldehyde with the guanidine group. The derivative was one-fourth as toxic as the native toxin. Modification of the guanidine side chain of Arg-13 with both 1,2-cyclohexanedione and phenylglyoxal decreased the toxicity of RTX-III by a factor of five. We conclude that Arg-13 is not fully responsible for toxicity. The toxin-receptor attachment might be multipoint, involving several structural elements of the protein molecule, with Arg-13, probably being one of them. The guanidine side chain of Arg-45 is buried in the sequence and apparently functionally nonessential.