The effect of tryptophan modification on the structure and function of a sea snake neurotoxin

M Allen and AT Tu

A neurotoxin has been isolated from the venom of the sea snake Lapemis hardwickii. This neurotoxin contains only one tryptophan residue which was chemically modified with two different reagents, 2-hydroxy-5- nitrobenzyl bromide and N-bromosuccinimide. Following modification, the neurotoxin almost completely lost its acetylcholine receptor-binding activity. To examine the effect tryptophan modification had on the conformation of the neurotoxin, circular dichroic and Raman spectra were taken of the modified neurotoxin and compared with those of the native toxin. The overall conformation of the modified neurotoxin was very similar to the native conformation. The Raman data also indicated some side chain conformations in the modified toxin were very similar to those of the native toxin. These data suggest that the tryptophan in sea snake venom short chain neurotoxins may have a direct role in the acetylcholine receptor binding process as well as a role in stabilizing the neurotoxin's active site in the proper conformation for optimum binding.

Volume 27, Issue 1, pp. 79-85, 01/01/1985
Copyright © 1985 by American Society for Pharmacology and Experimental Therapeutics