化学
代谢型谷氨酸受体
奎斯奎酸
兴奋剂
对接(动物)
立体化学
谷氨酸受体
代谢型谷氨酸受体1
氨基酸
生物化学
受体
甘氨酸
代谢受体
代谢型谷氨酸受体2
红藻氨酸
医学
护理部
作者
Hugues‐Olivier Bertrand,Anne‐Sophie Bessis,Jean‐Philippe Pin,Francine Acher
摘要
Several potent and group selective agonists of metabotropic glutamate receptors (mGluRs) have been docked at mGlu1,2,4R binding sites in the closed conformation of the bilobate extracellular domain. Quisqualic acid and (S)-3,5-dihydroxyphenylglycine (3,5-DHPG) were selected for mGlu1R, dicarboxycyclopropylglycine (DCG-IV), LY354740, (S)-4-carboxyphenylglycine (4CPG) for mGlu2R, and (S)-2-amino-4-phosphonobutyric acid (AP4), 1-aminocyclopentane-1,3,4-tricarboxylic acid (ACPT-I), (S)-4-phosphonophenylglycine (PPG) for mGlu4R. The models show a conserved binding pattern for the glycine moiety (α-amino and α-acidic functions) and group specific bindings for the distal acidic function. The best agonists allow optimized interaction with both lobes of the binding domain. Interlobe connections around the ligand are also described and participate in stabilizing the closed form of the amino-terminal domain. Altogether, the docking models support the proposal that the stabilization of a closed state represents a key step in agonist activation of mGluRs.
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