8RD9

human TRPM4 in SMA NBA

これはPDB形式変換不可エントリーです。

8RD9 の概要

• エントリーDOI: 10.2210/pdb8rd9/pdb
• EMDBエントリー: 19069
• 分子名称: Transient receptor potential cation channel subfamily M member 4, 4-chloranyl-2-(2-naphthalen-1-yloxyethanoylamino)benzoic acid, CHOLESTEROL (3 entities in total)
• 機能のキーワード: trpm, inhibitor, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 340635.10

構造登録者

Ekundayo, B.,Prakash, A.,Christian, G.,Anne, F.H.,Sabrina, G.,Mey, B.,Daniela, R.,Martin, L.,Jean, S.R.,Henning, S.,Hugues, A.,Dongchun, N. (登録日: 2023-12-07, 公開日: 2024-12-18, 最終更新日: 2025-02-05)

主引用文献

Ekundayo, B.,Arullampalam, P.,Gerber, C.E.,Hammerli, A.F.,Guichard, S.,Boukenna, M.,Ross-Kaschitza, D.,Lochner, M.,Rougier, J.S.,Stahlberg, H.,Abriel, H.,Ni, D.
Identification of a binding site for small molecule inhibitors targeting human TRPM4.
Nat Commun, 16:833-833, 2025

PubMed Abstract: Transient receptor potential (TRP) melastatin 4 (TRPM4) protein is a calcium-activated monovalent cation channel associated with various genetic and cardiovascular disorders. The anthranilic acid derivative NBA is a potent and specific TRPM4 inhibitor, but its binding site in TRPM4 has been unknown, although this information is crucial for drug development targeting TRPM4. We determine three cryo-EM structures of full-length human TRPM4 embedded in native lipid nanodiscs without inhibitor, bound to NBA, and an anthranilic acid derivative, IBA. We found that the small molecules NBA and IBA were bound in a pocket formed between the S3, S4, and TRP helices and the S4-S5 linker of TRPM4. Our structural data and results from patch clamp experiments enable validation of a binding site for small molecule inhibitors, paving the way for further drug development targeting TRPM4.

PubMed: 39828793
DOI: 10.1038/s41467-025-56131-2

実験手法

ELECTRON MICROSCOPY (4.3 Å)