Labbé-Jullié C, Granier C, Albericio F, Defendini M L, Ceard B, Rochat H, Van Rietschoten J
Centre National de la Recherche Scientifique UA 1179, Faculté de Médecine Secteur Nord, Marseille, France.
Eur J Biochem. 1991 Mar 28;196(3):639-45. doi: 10.1111/j.1432-1033.1991.tb15860.x.
The structural features of apamin, a natural octadecapeptide from bee venom, enabling binding to its receptor and the expression of toxicity in mice, have been delineated by studying the effects on binding and toxicity of chemical modifications and amino acid substitutions in synthetic analogues. The results obtained indicate that the only hydrophobic residue, leucine at position 10, can be changed to alanine without a significant decrease in the specific activity. The need for a correct conformation has been established and also the importance of Gln-17 and the side chains of Arg-13 and Arg-14 (besides the charge effects). The interaction of apamin with its receptor, a calcium-activated potassium channel, is thus mediated by a precise topology around these three residues. Due to the ability to detect very low specific activities for some of the analogues, it has been shown that, individually, none of these interactions constitute an essential criteria for binding per se, but that their presence is necessary for the high specific activity of the toxin.
通过研究化学修饰和合成类似物中氨基酸取代对结合和毒性的影响，已经阐明了蜂毒明肽（一种来自蜂毒的天然十八肽）的结构特征，这些特征使其能够与其受体结合并在小鼠中表现出毒性。所得结果表明，唯一的疏水残基，即第10位的亮氨酸，可以被丙氨酸取代而不会显著降低比活性。已经确定了正确构象的必要性，以及Gln-17以及Arg-13和Arg-14侧链（除电荷效应外）的重要性。因此，蜂毒明肽与其受体（一种钙激活钾通道）的相互作用是由这三个残基周围的精确拓扑结构介导的。由于能够检测到某些类似物的极低比活性，已经表明，单独来看，这些相互作用中没有一个本身构成结合的必要标准，但它们的存在对于毒素的高比活性是必要的。
