Conformation and location of membrane-bound salinomycin-sodium complex deduced from NMR in isotropic bicelles.
Conformation and location of membrane-bound salinomycin-sodium complex deduced from NMR in isotropic bicelles.
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DOI：
10.1021/ja075024l
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发表时间：
2007-11
影响因子：
15
通讯作者：
N. Matsumori;Atsushi Morooka;M. Murata
中科院分区：
文献类型：
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作者：
N. Matsumori;Atsushi Morooka;M. Murata
在由各向同性双分子层组成的膜环境中对离子载体抗生素盐霉素进行了研究，双分子层是比胶束更好的生物膜模型，并且确定了盐霉素在双分子层中的构象和拓扑取向。二维核磁共振测量和受限构象搜索表明，双分子层中的盐霉素钠盐采用一种开放构象，其中E环的取向与晶体和溶液结构中的取向显著不同。这种构象改变打破了28 - OH和1 - O之间的分子内氢键，使E环的醚氧从晶体中观察到的与钠离子的配位位置发生位移，从而削弱了盐霉素与钠离子之间的络合。使用多西磷酯进行的顺磁弛豫实验表明，盐霉素浅嵌于双分子层中，两端更靠近水界面，烯烃部分面向双分子层内部。盐霉素与磷脂之间的分子间核奥弗豪泽效应（NOE）测量进一步支持了这种取向。与钠离子较弱的络合以及在膜极性区域的位置偏好可能促进金属离子在双层膜的极性/非极性界面的捕获和释放。基于这些发现，提出了一个盐霉素辅助金属离子跨生物膜运输的模型。
An ionophore antibiotic salinomycin was studied in a membrane environment consisting of isotropic bicelles, a better model for biological membranes than micelles, and its conformation and topological orientation in bicelles was determined. 2D NMR measurements and restrained conformational search revealed that salinomycin-sodium salt in bicelles adopts an open conformation in which the orientation of the E-ring is significantly different from that in crystal and solution structures. This conformational alteration breaks an intramolecular hydrogen bond between 28-OH and 1-O, dislocates the ether oxygen of the E-ring from a coordinated position to the sodium ion observed in the crystal, and consequently weakens the complexation between salinomycin and the sodium ion. Paramagnetic relaxation experiments using doxyl-phospholipids reveal that salinomycin is embedded shallowly in bicelles, with both terminals being closer to the water interface and the olefin portion facing the bicelle interior. Measurements of intermolecular NOEs between salinomycin and phospholipids further supported this orientation. Weaker complexation with sodium ion and positional preference in the membrane polar region may facilitate the catch-and-release of metal ions at the polar/nonpolar interface of bilayers. On the basis of these findings, a model for salinomycin-assisted transport of metal ions across biological membranes is proposed.