Chemical modification of arginine residues in alpha-bungarotoxin.
The reaction of alpha-bungarotoxin (alpha-BuTX) with 1,2-cyclohexanedione resulted in the modification of only Arg-72 but arginine at position 36 or 72, as well as both were modified by reaction of the toxin with p-hydroxyphenylglyoxal. No derivative modified at Arg-25 was obtained, indicating that this residue may be located in the interior region of alpha-BuTX molecule. Monoderivative at Arg-72 showed about 50% of the lethal toxicity and binding activity of alpha-BuTX to nicotinic acetylcholine receptor (AChR), while the activity was decreased to one-third when the invariant Arg-36 was modified, indicating that the latter residue is more closely related to the interaction of the toxin with AChR. Approx. 13% of the residual activity was observed when both arginine residues at 36 and 72 were modified. The antigenicity of alpha-BuTX was still retained essentially intact after Arg-36 or -72 was modified, whereas it decreased to 50% when both these arginine residues were modified. The present study indicates that Arg-36 and -72 in alpha-BuTX may be involved in the multipoint contact between the toxin and AChR, but neither is absolutely essential for the binding.
Lin
S R
SR
Department of Chemistry, Kaohsiung Medical College, Taiwan, ROC.
Chang
C C
CC
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001120:Arginine / Q000032:analysis; D001665:Binding Sites; D002038:Bungarotoxins / Q000737:chemistry / Q000276:immunology / Q000633:toxicity*; D005260:Female; D008297:Male; D051379:Mice; D011950:Receptors, Cholinergic / Q000378:metabolism; D013329:Structure-Activity Relationship
D000596:Amino Acids; D002038:Bungarotoxins; D011950:Receptors, Cholinergic; D001120:Arginine