7KAA

NMR solution structures of tirasemtiv drug bound to a fast skeletal troponin C-troponin I complex

7KAA の概要

• エントリーDOI: 10.2210/pdb7kaa/pdb
• NMR情報: BMRB: 30801
• 分子名称: Troponin C, skeletal muscle,Troponin I, fast skeletal muscle chimera, CALCIUM ION, 6-ethynyl-1-(pentan-3-yl)-1H-imidazo[4,5-b]pyrazin-2-ol (3 entities in total)
• 機能のキーワード: activator, contractile protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17366.98

構造登録者

Mercier, P.,Li, M.X.,Hartman, J.J.,Sykes, B.D. (登録日: 2020-09-30, 公開日: 2021-03-24, 最終更新日: 2024-05-15)

主引用文献

Li, M.X.,Mercier, P.,Hartman, J.J.,Sykes, B.D.
Structural Basis of Tirasemtiv Activation of Fast Skeletal Muscle.
J.Med.Chem., 64:3026-3034, 2021

PubMed Abstract: Troponin regulates the calcium-mediated activation of skeletal muscle. Muscle weakness in diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy occurs from diminished neuromuscular output. The first direct fast skeletal troponin activator, , amplifies the response of muscle to neuromuscular input. binds selectively and strongly to fast skeletal troponin, slowing the rate of calcium release and sensitizing muscle to calcium. We report the solution NMR structure of bound to a fast skeletal troponin C-troponin I chimera. The structure reveals that binds in a hydrophobic pocket between the regulatory domain of troponin C and the switch region of troponin I, which overlaps with that of Anapoe in the X-ray structure of skeletal troponin. Multiple interactions stabilize the troponin C-troponin I interface, increase the affinity of troponin C for the switch region of fast skeletal troponin I, and drive the equilibrium toward the active state.

PubMed: 33703886
DOI: 10.1021/acs.jmedchem.0c01412

実験手法

SOLUTION NMR