7YG5

Structure of human R-type voltage-gated CaV2.3-alpha2/delta1-beta1 channel complex in the topiramate-bound state

7YG5 の概要

• エントリーDOI: 10.2210/pdb7yg5/pdb
• EMDBエントリー: 33808
• 分子名称: Voltage-dependent R-type calcium channel subunit alpha-1E, [(3aS,5aR,8aR,8bS)-2,2,7,7-tetramethyltetrahydro-3aH-bis[1,3]dioxolo[4,5-b:4',5'-d]pyran-3a-yl]methyl sulfamate, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• 機能のキーワード: voltage-gated calcium channel, cav2.3, complex, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 463732.16

構造登録者

Gao, Y.,Zhao, Y. (登録日: 2022-07-11, 公開日: 2023-11-29, 最終更新日: 2024-07-03)

主引用文献

Gao, Y.,Bai, Q.,Zhang, X.C.,Zhao, Y.
Structural insights into the allosteric effects of the antiepileptic drug topiramate on the Ca V 2.3 channel.
Biochem.Biophys.Res.Commun., 725:150271-150271, 2024

PubMed Abstract: The R-type voltage-gated calcium channel Ca2.3 is predominantly located in the presynapse and is implicated in distinct types of epileptic seizures. It has consequently emerged as a molecular target in seizure treatment. Here, we determined the cryo-EM structure of the Ca2.3-α2δ1-β1 complex in the topiramate-bound state at a 3.0 Å resolution. We provide a snapshot of the binding site of topiramate, a widely prescribed antiepileptic drug, on a voltage-gated ion channel. The binding site is located at an intracellular juxtamembrane hydrophilic cavity. Further structural analysis revealed that topiramate may allosterically facilitate channel inactivation. These findings provide fundamental insights into the mechanism underlying the inhibitory effect of topiramate on Ca and Na channels, elucidating a previously unseen modulator binding site and thus pointing toward a route for the development of new drugs.

PubMed: 38901222
DOI: 10.1016/j.bbrc.2024.150271

実験手法

ELECTRON MICROSCOPY (3 Å)