6FLR

Super-open structure of the AMPAR GluA3 N-terminal domain

6FLR の概要

• エントリーDOI: 10.2210/pdb6flr/pdb
• 分子名称: Glutamate receptor 3, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: ligand-gated ion channel, membrane protein, ampa receptor
• 由来する生物種: Rattus norvegicus (Rat)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 91035.59

構造登録者

Garcia-Nafria, J. (登録日: 2018-01-27, 公開日: 2018-12-19, 最終更新日: 2024-11-13)

主引用文献

Lee, J.Y.,Krieger, J.,Herguedas, B.,Garcia-Nafria, J.,Dutta, A.,Shaikh, S.A.,Greger, I.H.,Bahar, I.
Druggability Simulations and X-Ray Crystallography Reveal a Ligand-Binding Site in the GluA3 AMPA Receptor N-Terminal Domain.
Structure, 27:241-252.e3, 2019

PubMed Abstract: Ionotropic glutamate receptors (iGluRs) mediate the majority of excitatory neurotransmission in the brain. Their dysfunction is implicated in many neurological disorders, rendering iGluRs potential drug targets. Here, we performed a systematic analysis of the druggability of two major iGluR subfamilies, using molecular dynamics simulations in the presence of drug-like molecules. We demonstrate the applicability of druggability simulations by faithfully identifying known agonist and modulator sites on AMPA receptors (AMPARs) and NMDA receptors. Simulations produced the expected allosteric changes of the AMPAR ligand-binding domain in response to agonist. We also identified a novel ligand-binding site specific to the GluA3 AMPAR N-terminal domain (NTD), resulting from its unique conformational flexibility that we explored further with crystal structures trapped in vastly different states. In addition to providing an in-depth analysis into iGluR NTD dynamics, our approach identifies druggable sites and permits the determination of pharmacophoric features toward novel iGluR modulators.

PubMed: 30528594
DOI: 10.1016/j.str.2018.10.017

実験手法

X-RAY DIFFRACTION (2.51 Å)