le Du M H, Marchot P, Bougis P E, Fontecilla-Camps J C
Laboratoire de Cristallographie et Cristallogénèse des Protéines, Département d'Ingéniérie et d'Etudes des Protéines, DSV, CENG, Grenoble, France.
J Biol Chem. 1992 Nov 5;267(31):22122-30. doi: 10.2210/pdb1fas/pdb.
The crystal structure of fasciculin 1, a potent acetylcholinesterase inhibitor from green mamba snake venom, has been solved by the multiple isomorphous replacement method complemented with anomalous scattering and subsequently refined at 1.9-A resolution. The overall structure of fasciculin is similar to those of the short alpha-neurotoxins and cardiotoxins, with a dense core rich in disulfide bridges and three long loops disposed as the central fingers of a hand. A comparison of these three prototypic toxin types shows that fasciculin 1 has structural features that are intermediate between those of the other two molecules. Its core region, which can be defined as a continuous stretch of conserved residues, is very similar to that of erabutoxin b, whereas the orientation of its long loops resembles that of cardiotoxin VII4. This result introduces a new element in the study of phylogenetic relationships of snake toxins and suggests that, after divergency from an ancestral gene, convergent evolution may have played an important factor in the evolution of these proteins. In fasciculin 1, several arginine and lysine residues are well ordered and relatively exposed to the solvent medium and may play a role in the binding to the peripheral site of acetylcholinesterases.
绿曼巴蛇毒中一种强效乙酰胆碱酯酶抑制剂——束丝菌素1的晶体结构，已通过多重同晶置换法并辅以反常散射得以解析，随后在1.9埃分辨率下进行了精修。束丝菌素的整体结构与短α-神经毒素和心脏毒素相似，有一个富含二硫键的致密核心以及三条长环，排列成手的中央手指状。对这三种典型毒素类型的比较表明，束丝菌素1具有介于其他两种分子之间的结构特征。其核心区域可定义为一段连续的保守残基，与 erabutoxin b的核心区域非常相似，而其长环的取向则类似于心脏毒素VII4。这一结果为蛇毒素系统发育关系的研究引入了一个新元素，并表明在从祖先基因分化后，趋同进化可能在这些蛋白质的进化中起到了重要作用。在束丝菌素1中，几个精氨酸和赖氨酸残基排列有序且相对暴露于溶剂介质中，可能在与乙酰胆碱酯酶外周位点的结合中发挥作用。
