The vesicular glutamate transporters (VGLUTs) bind and move glutamate (Glu) from the cytosol into the lumen of synaptic vesicles using a H+-electrochemical gradient (ΔpH and Δψ) generated by the vesicular H+-ATPase. VGLUTs show very low Glu binding and to date, no three-dimensional structure has been elucidated. Prior studies have attempted to identify the key residues involved in binding VGLUT substrates and inhibitors using homology models and docking experiments. Recently, the inward and outward oriented crystal structures of d-galactonate transporter (DgoT) emerged as possible structure templates for VGLUT. In this review, a new homology model for VGLUT2 based on DgoT has been developed and used to conduct docking experiments to identify and differentiate residues and binding orientations involved in ligand interactions. This review describes small molecule-ligand interactions including docking using a VGLUT2 homology model derived from DgoT.

中文翻译：

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VGLUT底物和抑制剂：计算角度。

囊泡谷氨酸转运蛋白（VGLUTs）利用囊泡H + -ATPase产生的H +-电化学梯度（ΔpH和Δψ）将谷氨酸（Glu）从胞质溶胶中转移到突触囊泡腔中。VGLUT显示出非常低的Glu结合力，迄今为止，尚未阐明三维结构。先前的研究已经尝试使用同源性模型和对接实验来鉴定参与结合VGLUT底物和抑制剂的关键残基。最近，d-半乳糖酸酯转运蛋白（DgoT）的向内和向外取向的晶体结构作为VGLUT的可能结构模板出现。在这篇综述中，基于DgoT的VGLUT2的新同源性模型已被开发出来，并用于进行对接实验，以鉴定和区分参与配体相互作用的残基和结合方向。