西亚试剂：Neurotransmitter and psychostimulant recognition by the dop

Na+/Cl–-coupled biogenic amine transporters are the primary targets of therapeutic and abused drugs, ranging from antidepressants to the psychostimulants cocaine and amphetamines, and to their cognate substrates. Here we determine X-ray crystal structures of the Drosophila melanogaster dopamine transporter (dDAT) bound to its substrate dopamine, a substrate analogue 3,4-dichlorophenethylamine, the psychostimulants D-amphetamine and methamphetamine, or to cocaine and cocaine analogues. All ligands bind to the central binding site, located approximately halfway across the membrane bilayer, in close proximity to bound sodium and chloride ions. The central binding site recognizes three chemically distinct classes of ligands via conformational changes that accommodate varying sizes and shapes, thus illustrating molecular principles that distinguish substrates from inhibitors in biogenic amine transporters.

 多巴胺运输蛋白是一种膜蛋白，能将神经传输物质多巴胺从突触裂隙清除，将其运送到周围细胞的胞液内，从而终止神经传输物质的信号。Eric Gouaux及同事获得了与包括可卡因、右旋苯丙胺、甲基苯丙胺、多巴胺和两种抗抑郁剂在内的各种小分子结合在一起的果蝇多巴胺运输蛋白的X-射线晶体结构。除了让我们能够首次看到一种神经传输物质是怎样与一种生源胺运输蛋白相结合的、以及可卡因是怎样与一种生源胺运输蛋白相结合的外，该结构还是一种蛋白的配体结合点何以能够通过重塑自己来结合和适应具有不同形状和大小、在结构上不相关的小分子的一个很好例子。

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