Modification of arginine in sea anemone toxin RTX-III from Radianthus macrodactylus.
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.
Mahnir
V M
VM
Pacific Institute of Bioorganic Chemistry, Academy of Sciences of the U.S.S.R.
Kozlovskaya
E P
EP
Elyakov
G B
GB
D000447:Aldehydes; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine; D055598:Chemical Phenomena; D002621:Chemistry; D003064:Cnidarian Venoms / Q000633:toxicity*; D003512:Cyclohexanones; D051379:Mice; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000633:toxicity*; D010422:Pentanones; D010658:Phenylglyoxal; D012615:Sea Anemones / Q000032:analysis; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship
D000447:Aldehydes; D003064:Cnidarian Venoms; D003512:Cyclohexanones; D009498:Neurotoxins; D010422:Pentanones; C008790:acetylacetone; C018031:1,2-cyclohexanedione; D001120:Arginine; D010658:Phenylglyoxal