7TZC

A drug and ATP binding site in type 1 ryanodine receptor

これはPDB形式変換不可エントリーです。

7TZC の概要

• エントリーDOI: 10.2210/pdb7tzc/pdb
• EMDBエントリー: 26205
• 分子名称: Calmodulin-1, Peptidyl-prolyl cis-trans isomerase FKBP1A, Ryanodine receptor 1, ... (9 entities in total)
• 機能のキーワード: ryanodine receptor, calcium, ion channel, membrane protein-isomerase 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: 12
• 化学式量合計: 2392463.39

構造登録者

Melville, Z.,Dridi, H.,Yuan, Q.,Reiken, S.,Anetta, W.,Liu, Y.,Clarke, O.B.,Marks, A.R. (登録日: 2022-02-15, 公開日: 2022-05-18, 最終更新日: 2024-11-13)

主引用文献

Melville, Z.,Dridi, H.,Yuan, Q.,Reiken, S.,Wronska, A.,Liu, Y.,Clarke, O.B.,Marks, A.R.
A drug and ATP binding site in type 1 ryanodine receptor.
Structure, 30:1025-, 2022

PubMed Abstract: The ryanodine receptor (RyR)/calcium release channel on the sarcoplasmic reticulum (SR) is required for excitation-contraction coupling in skeletal and cardiac muscle. Inherited mutations and stress-induced post-translational modifications result in an SR Ca leak that causes skeletal myopathies, heart failure, and exercise-induced sudden death. A class of therapeutics known as Rycals prevent the RyR-mediated leak, are effective in preventing disease progression and restoring function in animal models, and are in clinical trials for patients with muscle and heart disorders. Using cryogenic-electron microscopy, we present a model of RyR1 with a 2.45-Å resolution before local refinement, revealing a binding site in the RY1&2 domain (3.10 Å local resolution), where the Rycal ARM210 binds cooperatively with ATP and stabilizes the closed state of RyR1.

PubMed: 35580609
DOI: 10.1016/j.str.2022.04.010

実験手法

ELECTRON MICROSCOPY (2.45 Å)