Darbon H
CNRS-UPR 9039, Institut de Biologie Structurale et Microbiologie, Marseille.
J Soc Biol. 1999;193(6):445-50.
Animal venoms contain various toxins which act on ion-channels, responsible for either sodium, potassium, calcium or chloride permeation. Structure determination of these toxins demonstrate that they are organised around two different structural motifs: potassium and sodium channel effectors are organised around an alpha-helix connected by two disulfide bridges to a two- or three-stranded beta sheet whereas calcium channels effectors are structured around an "Inhibitory Cystine Knot" motif made of a dense disulfide-rich core from which emerge several loops. Analysis of local structural modifications allows us to understand the structural basis of the selectivity of these effectors towards the various ion channels. This is the first step in the design of new synthetic molecules which are potent therapeutic drugs for diseases involving ion channel dysfunctioning.
动物毒液含有多种毒素,这些毒素作用于负责钠、钾、钙或氯渗透的离子通道。对这些毒素的结构测定表明,它们围绕两种不同的结构基序组织:钾通道和钠通道效应物围绕一个α-螺旋组织,该α-螺旋通过两个二硫键连接到一个两链或三链β-折叠,而钙通道效应物围绕一个“抑制性胱氨酸结”基序构建,该基序由一个密集的富含二硫键的核心组成,从该核心中伸出几个环。对局部结构修饰的分析使我们能够理解这些效应物对各种离子通道选择性的结构基础。这是设计新型合成分子的第一步,这些分子是治疗涉及离子通道功能障碍疾病的有效治疗药物。