Structure of glutamate analogs that activate the ON bipolar cell metabotropic glutamate receptor in vertebrate retina
Structure of glutamate analogs that activate the ON bipolar cell metabotropic glutamate receptor in vertebrate retina
复制标题
激活脊椎动物视网膜 ON 双极细胞代谢型谷氨酸受体的谷氨酸类似物的结构
作者：
N. Tian;M. Slaughter
虽然视网膜上有许多谷氨酸受体，但2-氨基-4-磷酸-丁酸(L-AP4)是选择性作用于双极细胞上代谢性谷氨酸受体(MGluR6)的激动剂。我们探索了激活这一受体的激动剂的特性。不同谷氨酸类似物对视网膜电波(ERG)b波的影响被用来衡量它们的活性。激动剂之间的构象比较表明，延长构象的配体优先与ON双极突触受体结合。但这一性质不足以解释mGluR6的选择性，因为一些不活跃的谷氨酸类似物也可以匹配这种延伸的构象。用比较分子场分析(CoMFA)比较激动剂在双极突触上的作用，比较激动剂的静电和空间位势。由三个假定的结合位点定义的平面下的空间位势在决定激动剂活性方面起着关键作用。CoMFA模型被用于预测谷氨酸类似物的活性，预测的活性与测量的活性之间的相关性支持该模型。
Although there are many glutamate receptors in the retina, 2-amino-4-phosphonobutyrate (L-AP4) is an agonist that acts selectively at metabotropic glutamate receptors (mGluR6) of ON bipolar cells. We explored the properties of agonists that activate this receptor. The effects of various glutamate analogs on the b-wave of the electroretinogram (ERG) were used as a measure of their activity. Conformational comparisons among agonists suggest that ligands in an extended conformation preferentially bind to the ON bipolar synaptic receptor. But this property is insufficient to explain the selectivity of mGluR6 because some inactive glutamate analogs could also match this extended conformation. Comparative molecular field analysis (CoMFA) was used to compare the electrostatic and steric potentials of agonists with their action at the ON bipolar synapse. Steric potentials beneath a plane defined by the three putative binding sites plays a key role in determining agonist activity. The CoMFA model was used to predict the activity of glutamate analogs and correlations between predicted and measured activity support the model.
人类免疫缺陷病毒（I）蛋白酶抑制剂的三维QSAR。
影响因子：
7.3
作者：
Waller,CL;Oprea,TI;Giolitti,A;Marshall,GR
通讯作者：
Marshall,GR
影响因子：
56.9
作者：
SLAUGHTER, MM;MILLER, RF
通讯作者：
MILLER, RF