Livingstone C D, Strange P G, Naylor L H
Biological Laboratory, The University, Canterbury, Kent, U.K.
Biochem J. 1992 Oct 1;287 ( Pt 1)(Pt 1):277-82. doi: 10.1042/bj2870277.
Three-dimensional computer models of the rat D2, D3 and D4 dopamine receptor subtypes have been constructed based on the diffraction co-ordinates for bacteriorhodopsin, another membrane-bound protein containing seven transmembrane domains presumed to be arranged in a similar spatial orientation. Models were assembled by aligning the putative transmembrane domains of the dopamine receptors with those of bacteriorhodopsin using sequence similarities, and then superimposing these modelled alpha-helices on to the bacteriorhodopsin-derived co-ordinates. These models explore the potential hydrogen bonding, electrostatic and stacking interactions within the receptor which may be important for maintaining the conformation of these receptors, and thereby provide target sites for agonist binding. Proposed interactions between the catecholamine ligands and these receptors appear to account for the affinity, although not the specificity, of these agonist ligands for the different dopamine receptor subtypes. Such models will be useful for establishing structure-function relationships between ligands and the dopamine receptors, and may ultimately provide a template for the design of receptor-specific drugs.
基于细菌视紫红质的衍射坐标构建了大鼠D2、D3和D4多巴胺受体亚型的三维计算机模型，细菌视紫红质是另一种膜结合蛋白，含有七个跨膜结构域，推测其以相似的空间取向排列。通过利用序列相似性将多巴胺受体的推定跨膜结构域与细菌视紫红质的跨膜结构域进行比对，然后将这些模拟的α螺旋叠加到源自细菌视紫红质的坐标上，从而组装模型。这些模型探索了受体内部潜在的氢键、静电和堆积相互作用，这些相互作用对于维持这些受体的构象可能很重要，从而为激动剂结合提供靶点。儿茶酚胺配体与这些受体之间的拟相互作用似乎解释了这些激动剂配体对不同多巴胺受体亚型的亲和力，但不是特异性。此类模型将有助于建立配体与多巴胺受体之间的结构-功能关系，并最终可能为受体特异性药物的设计提供模板。
