Identification of Edg1 receptor residues that recognize sphingosine 1-phosphate

作     者：Parrill, AL Wang, DA Bautista, DL Van Brocklyn, JR Lorincz, Z Fischer, DJ Baker, DL Liliom, K Spiegel, S Tigyi, G 

作者机构：Univ Tennessee Ctr Hlth Sci Dept Physiol Memphis TN 38163 USA Univ Memphis Dept Chem Memphis TN 38152 USA Univ Memphis Computat Res Mat Inst Memphis TN 38152 USA Ohio State Univ Dept Pathol Columbus OH 43210 USA Georgetown Univ Dept Biochem Washington DC 20007 USA 

出 版 物：《JOURNAL OF BIOLOGICAL CHEMISTRY》 (生物化学杂志)

年 卷 期：2000年第275卷第50期

页      面：39379-39384页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

基　　金：NHLBI NIH HHS [HL61469, HL07641] Funding Source: Medline NIGMS NIH HHS [GM43880] Funding Source: Medline 

主　　题：氨基酸序列 精氨酸/化学 结合部位 印迹法 蛋白质 细胞系 计算机模拟 谷氨酸/化学 即早蛋白质类/遗传学 即早蛋白质类/代谢 免疫组织化学 离子 配体 溶血磷脂素类 模型 分子 分子序列数据 诱变 定点 突变 蛋白质结合 蛋白质结构 二级 受体 细胞表面/代谢 受体 G-蛋白偶联 受体 溶血磷脂 序列同源性 氨基酸 鞘氨醇/类似物和衍生物 鞘氨醇/遗传学 鞘氨醇/代谢 转染 肿瘤细胞 培养的 动物 人类 大鼠 

摘      要：Originating from its DNA sequence, a computational model of the Edg1 receptor has been developed that predicts critical interactions with its ligand, sphingosine I-phosphate. The basic amino acids Arg(120) and Arg(292) ion pair with the phosphate, whereas the acidic Glu(121) residue ion pairs with the ammonium moiety of sphingosine l-phosphate. The requirement of these interactions for specific ligand recognition has been confirmed through examination of site-directed mutants by radioligand binding, ligand-induced [S-35]GTP gammaS binding, and receptor internalization assays. These ion-pairing interactions explain the ligand specificity of the Edg1 receptor and provide insight into ligand specificity differences within the Edg receptor family. This computational map of the ligand binding pocket provides information necessary for understanding the molecular pharmacology of this receptor, thus underlining the potential of the computational method in predicting ligand-receptor interactions.