Specific binding of cinnamycin (Ro 09-0198) to phosphatidylethanolamine. Comparison between micellar and membrane environments
Specific binding of cinnamycin (Ro 09-0198) to phosphatidylethanolamine. Comparison between micellar and membrane environments
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DOI：
10.1021/bi035225b
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发表时间：
2003-11-04
期刊：
影响因子：
2.9
通讯作者：
Seelig, J
中科院分区：
文献类型：
--
作者：
Machaidze, G;Seelig, J
肉桂霉素（Ro 09-0198）是一种四环肽类抗生素，可与磷脂酰乙醇胺（PE）特异性结合。与磷脂酰乙醇胺的复合物的形成遵循1：1的化学计量。使用高灵敏度等温滴定量热法（ITC），我们已经测量了两种不同的PE环境，即，无论是在辛基葡糖苷（OG）胶束或在1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱（POPC）双层膜溶解的PE络合物形成的热力学参数。我们比较了二酰基-PE与溶血-PE，并将碳链长度从6改变到18。结合需要PE头基和至少一个脂肪酰基链。形成络合物的最佳链长（n）为8。较长的链不会增强结合亲和力;对于较短的链，相互作用减弱。肉桂霉素-PE复合物在POPC膜中的结合常数K-0约为10（7）~ 10（8）M-1，而在辛基葡糖苷胶束中的结合常数K-0仅约为10（6）M-1。这种差异可归因于肉桂霉素与脂质膜的非特异性疏水相互作用。复合物的形成在OG胶束中是焓驱动的，而在双层膜中焓和熵做出相等的贡献。然而，对于8的最佳链长（n），双层膜的结合反应也是完全非线性驱动的。
Cinnamycin (Ro 09-0198) is a tetracyclic peptide antibiotic that binds specifically to phosphatidylethanolamine (PE). Formation of a complex with phosphatidylethanolamine follows a 1:1 stoichiometry. Using high-sensitivity isothermal titration calorimetry (ITC), we have measured the thermodynamic parameters of complex formation for two different PE environments, namely, PE dissolved either in octyl glucoside (OG) micelles or in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer membrane. We have compared diacyl-PE with lyso-PE and have varied the carbon chain length from 6 to 18. Binding requires both a PE headgroup and at least one fatty acyl chain. The optimum chain length for complex formation (n) is eight. Longer chains do not enhance the binding affinity; for shorter chains, the interaction is weakened. The cinnamycin-PE complex has a binding constant K-0 of similar to10(7)-10(8) M-1 in the POPC membrane and only similar to10(6) M-1 in the octyl glucoside micelle. The difference can be attributed to the nonspecific hydrophobic interaction of cinnamycin with the lipid membrane. Complex formation is enthalpy-driven in OG micelles, whereas enthalpy and entropy make equal contributions in bilayer membranes. However, for the optimum chain length (n) of eight, the binding reaction is also completely enthalpy-driven for the bilayer membrane.