Structural dynamics of the monoamine transporter homolog LeuT from accelerated conformational sampling and channel analysis.
Structural dynamics of the monoamine transporter homolog LeuT from accelerated conformational sampling and channel analysis.
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DOI：
10.1002/prot.24588
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发表时间：
2014-10
影响因子：
2.9
通讯作者：
Madura, Jeffry D.
中科院分区：
文献类型：
--
作者：
Thomas, James R.;Gedeon, Patrick C.;Madura, Jeffry D.
细菌亮氨酸转运蛋白LeuT与人类单胺转运蛋白（MAT）如多巴胺和5-羟色胺再摄取蛋白保持着显著的二级结构相似性。MAT的计算研究的主要方法是通过使用结晶的LeuT结构。LeuT的不同构象可以深入了解MAT家族的机制细节。通过加速分子动力学（aMD）模拟测试亮氨酸底物和结合的钠离子的不同组合进行的构象采样揭示了七个不同的构象簇。已经进行了进一步的分析，以靶向盐桥残基R30-D404、Y108-F253和R5-D369以及七个分离结构和总轨迹上的跨膜结构域。此外，溶剂的可及性LeuT和它的底物结合口袋已被分析使用的程序计算通道半径。占据Na 2位点稳定了外向构象，并且应该在亮氨酸和Na 1钠之前结合到开放的外向构象，同时发现两种可能的途径可用于细胞内转运。
The bacterial leucine transporter LeuT retains significant secondary structure similarities to the human monoamine transporters (MAT) such as the dopamine and serotonin reuptake proteins. The primary method of computational study of the MATs has been through the use of the crystallized LeuT structure. Different conformations of LeuT can give insight into mechanistic details of the MAT family. A conformational sampling performed through accelerated molecular dynamics (aMD) simulations testing different combinations of the leucine substrate and bound sodium ions revealed seven distinct conformational clusters. Further analysis has been performed to target salt-bridge residues R30–D404, Y108–F253, and R5–D369 and transmembrane domains on both the seven isolated structures and the total trajectories. In addition, solvent accessibility of LeuT and its substrate binding pockets has been analyzed using a program for calculating channel radii. Occupation of the Na2 site stabilizes the outward conformation and should bind to the open outward conformation before the leucine and Na1 sodium while two possible pathways were found to be available for intracellular transport.
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影响因子：
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