5VDI

Crystal Structure of Human Glycine Receptor alpha-3 Mutant N38Q Bound to AM-3607, Glycine, and Ivermectin

5VDI の概要

• エントリーDOI: 10.2210/pdb5vdi/pdb
• 関連するPDBエントリー: 5VDH
• 分子名称: Glycine receptor subunit alpha-3, (3S,3aS,9bS)-2-[(2H-1,3-benzodioxol-5-yl)sulfonyl]-3,5-dimethyl-1,2,3,3a,5,9b-hexahydro-4H-pyrrolo[3,4-c][1,6]naphthyridin-4-one, GLYCINE, ... (6 entities in total)
• 機能のキーワード: ligand-gated ion channel, neurotransmitter receptor, membrane protein, cys-loop receptor, transport protein
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cell junction, synapse, postsynaptic cell membrane ; Multi-pass membrane protein : O75311
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 216442.15

構造登録者

Shaffer, P.L.,Huang, X.,Chen, H. (登録日: 2017-04-03, 公開日: 2017-05-24, 最終更新日: 2023-10-04)

主引用文献

Huang, X.,Chen, H.,Shaffer, P.L.
Crystal Structures of Human GlyR alpha 3 Bound to Ivermectin.
Structure, 25:945-950.e2, 2017

PubMed Abstract: Ivermectin acts as a positive allosteric modulator of several Cys-loop receptors including the glutamate-gated chloride channels (GluCls), γ-aminobutyric acid receptors (GABARs), glycine receptors (GlyRs), and neuronal α7-nicotinic receptors (α7 nAChRs). The crystal structure of Caenorhabditis elegans GluCl complexed with ivermectin revealed the details of its ivermectin binding site. Although the electron microscopy structure of zebrafish GlyRα1 complexed with ivermectin demonstrated a similar binding orientation, detailed structural information on the ivermectin binding and pore opening for Cys-loop receptors in vertebrates has been elusive. Here we present the crystal structures of human GlyRα3 in complex with ivermectin at 2.85 and 3.08 Å resolution. Our structures allow us to explore in detail the molecular recognition of ivermectin by GlyRs, GABARs, and α7 nAChRs. Comparisons with previous structures reveal how the ivermectin binding expands the ion channel pore. Our results hold promise in structure-based design of GlyR modulators for the treatment of neuropathic pain.

PubMed: 28479061
DOI: 10.1016/j.str.2017.04.007

実験手法

X-RAY DIFFRACTION (3.1 Å)