Substrate binding and formation of an occluded state in the leucine transporter
Substrate binding and formation of an occluded state in the leucine transporter
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DOI：
10.1529/biophysj.107.117580
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发表时间：
2008-03-01
影响因子：
3.4
通讯作者：
Tajkhorshid, Ernad
中科院分区：
文献类型：
--
作者：
Celik, Leyla;Schiott, Birgit;Tajkhorshid, Ernad
用分子动力学模拟方法研究了亮氨酸转运蛋白(Leut)的前庭转运和亮氨酸结合。S对亮氨酸、结合底物和结合结构Na+离子的不同组合进行了0.1MU以上的全原子分子动力学模拟，描述了参与底物结合和闭锁态形成的分子事件，并研究了这种状态的动力学。三个结构特征被发现直接参与亮氨酸运输的初始步骤：一个Na+离子直接与亮氨酸配位(Na-1)，两个靠近细胞外前庭结合部位的芳香族残基(Tyr-108和Phe-253)，以及细胞外前庭中的盐桥(Arg-30和Asp-404)。这些特征解释了在有和没有结合底物的Leut模拟之间观察到的差异，以及亮氨酸结合的可能途径，从而形成封闭的Leut结合位点。
Translocation through the extracellular vestibule and binding of leucine in the leucine transporter (LeuT) have been studied with molecular dynamics simulations. More than 0.1 mu s of all-atom molecular dynamics simulations have been performed on different combinations of LeuT, bound substrate, and bound structural Na+ ions to describe molecular events involved in substrate binding and in the formation of the occluded state and to investigate the dynamics of this state. Three structural features are found to be directly involved in the initial steps of leucine transport: a Na+ ion directly coordinated to leucine (Na-1), two aromatic residues closing the binding site toward the extracellular vestibule (Tyr-108 and Phe-253), and a salt bridge in the extracellular vestibule (Arg-30 and Asp-404). These features account for observed differences between simulations of LeuT with and without bound substrate and for a possible pathway for leucine binding and thereby formation of the occluded LeuT binding site.