Structure-function relationships of scorpion neurotoxins.
Structure-function relationships of scorpion neurotoxins.
复制标题
蝎子神经毒素的结构-功能关系。
DOI：
10.1021/bi00656a002
复制
发表时间：
1976
期刊：
影响因子：
2.9
通讯作者：
F. Sampieri
中科院分区：
文献类型：
--
作者：
C. Habersetzer;F. Sampieri
对南雄蝎子毒素I、II和III中的一些三功能氨基酸残基进行了化学修饰。结果表明：(1)一个二硫桥的还原和甲基化破坏了毒素II的毒性活性。(2)毒素II唯一的色氨酸残基（位置38）不包含在分子的活性位点。(3)对毒素II中含有的7种羧酸酯中的5种进行修饰后，毒性活性得到抑制。(4)毒素II中赖氨酸和酪氨酸残基的乙酰化导致毒性和抗原活性的丧失。用羟胺处理乙酰化毒素可部分恢复抗原活性。在毒素I的情况下，总乙酰化只消除毒性活性。因此，至少有一个酪氨酸残基参与了毒素II的抗原位点。(5)毒素II和III的Citraconylation导致毒性完全丧失；癸丙基化恢复全部活性。(6)毒素II的胍基化对其毒性影响不显著。(7)碘乙酸对毒素II的烷基化对氨基和组氨酸残基都有影响。毒性的丧失主要是由于赖氨酸残基的修饰。在毒素I的情况下，毒性损失的动力学与一个赖氨酸残基的共价修饰密切相似。
Chemical modification of some trifunctional amino acid residues in toxins I, II, and III of the scorpion Androctonus australis Hector have been performed. The results indicate: (1) Reduction and methylation of one disulfide bridge destroy toxic activity of toxin II. (2) The only tryptophan residue of toxin II (position 38) is not included in the active site of the molecule. (3) Modification of five carboxylates out of the seven contained in toxin II suppresses the toxic activity. (4) Acetylation of the lysine and tyrosine residues in toxin II leads to the loss of both toxic and antigenic activity. Treatment of the acetylated toxin by hydroxylamine restores partially the antigenic activity. In the case of toxin I, total acetylation abolishes only the toxic activity. It is concluded that at least one tyrosine residue must be involved in an antigenic site of toxin II. (5) Citraconylation of toxins II and III leads to complete loss of toxicity; decitraconylation restores full activity. (6) Guanidination of toxin II does not affect its toxicity significantly. (7) Alkylation of toxin II by iodoacetic acid affects both amino groups and histidine residues. The loss of toxicity is mainly due to the modification of the lysine residues. In the case of toxin I, the kinetics of toxicity loss closely parallel the covalent modification of one lysine residue.