7WIT

Structure of SUR1 in complex with mitiglinide

7WIT の概要

• エントリーDOI: 10.2210/pdb7wit/pdb
• EMDBエントリー: 32535
• 分子名称: ATP-sensitive inward rectifier potassium channel 11,ATP-binding cassette sub-family C member 8 isoform X1, ADENOSINE-5'-TRIPHOSPHATE, (2S)-4-[(3aR,7aS)-1,3,3a,4,5,6,7,7a-octahydroisoindol-2-yl]-4-oxidanylidene-2-(phenylmethyl)butanoic acid (3 entities in total)
• 機能のキーワード: sur1, katp, channel, mitiglinide, membrane protein
• 由来する生物種: Bos taurus (cattle); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 160262.43

構造登録者

Chen, L.,Wang, M.M. (登録日: 2022-01-04, 公開日: 2022-11-16, 最終更新日: 2025-07-02)

主引用文献

Wang, M.M.,Wu, J.X.,Chen, L.
Structural Insights Into the High Selectivity of the Anti-Diabetic Drug Mitiglinide
Front Pharmacol, 13:929684-929684, 2022

PubMed Abstract: Mitiglinide is a highly selective fast-acting anti-diabetic drug that induces insulin secretion by inhibiting pancreatic K channels. However, how mitiglinide binds K channels remains unknown. Here, we show the cryo-EM structure of the SUR1 subunit complexed with mitiglinide. The structure reveals that mitiglinide binds inside the common insulin secretagogue-binding site of SUR1, which is surrounded by TM7, TM8, TM16, and TM17. Mitiglinide locks SUR1 in the NBD-separated inward-facing conformation. The detailed structural analysis of the mitiglinide-binding site uncovers the molecular basis of its high selectivity.

PubMed: 35847046
DOI: 10.3389/fphar.2022.929684

実験手法

ELECTRON MICROSCOPY (3.21 Å)