3LSF

Piracetam bound to the ligand binding domain of GluA2

3LSF の概要

• エントリーDOI: 10.2210/pdb3lsf/pdb
• 関連するPDBエントリー: 3LSL 3LSW 3LSX
• 分子名称: Glutamate receptor 2, GLUTAMIC ACID, 2-(2-oxopyrrolidin-1-yl)acetamide, ... (5 entities in total)
• 機能のキーワード: glutamate receptor, glur2, glua2, ampa receptor, neurotransmitter receptor, s1s2, allosteric modulator, alternative splicing, cell junction, cell membrane, endoplasmic reticulum, glycoprotein, ion transport, ionic channel, membrane, phosphoprotein, postsynaptic cell membrane, receptor, rna editing, synapse, transmembrane, transport, transport protein
• 由来する生物種: Rattus norvegicus (brown rat,rat,rats); 詳細
• 細胞内の位置: Cell membrane; Multi-pass membrane protein: P19491
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 88046.26

構造登録者

Ahmed, A.H.,Ptak, C.P.,Oswald, R.E. (登録日: 2010-02-12, 公開日: 2010-03-16, 最終更新日: 2024-10-30)

主引用文献

Ahmed, A.H.,Oswald, R.E.
Piracetam Defines a New Binding Site for Allosteric Modulators of alpha-Amino-3-hydroxy-5-methyl-4-isoxazole-propionic Acid (AMPA) Receptors.
J.Med.Chem., 53:2197-2203, 2010

PubMed Abstract: Glutamate receptors are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system and are important potential drug targets for cognitive enhancement and the treatment of schizophrenia. Allosteric modulators of AMPA receptors promote dimerization by binding to a dimer interface and reducing desensitization and deactivation. The pyrrolidine allosteric modulators, piracetam and aniracetam, were among the first of this class of drugs to be discovered. We have determined the structure of the ligand binding domain of the AMPA receptor subtypes GluA2 and GluA3 with piracetam and a corresponding structure of GluA3 with aniracetam. Both drugs bind to GluA2 and GluA3 in a very similar manner, suggesting little subunit specificity. However, the binding sites for piracetam and aniracetam differ considerably. Aniracetam binds to a symmetrical site at the center of the dimer interface. Piracetam binds to multiple sites along the dimer interface with low occupation, one of which is a unique binding site for potential allosteric modulators. This new site may be of importance in the design of new allosteric regulators.

PubMed: 20163115
DOI: 10.1021/jm901905j

実験手法

X-RAY DIFFRACTION (1.851 Å)