9C0Y

Clathrin terminal domain complexed with Pitstop 2c

これはPDB形式変換不可エントリーです。

9C0Y の概要

• エントリーDOI: 10.2210/pdb9c0y/pdb
• 分子名称: Clathrin heavy chain 1, DIMETHYL SULFOXIDE, DI(HYDROXYETHYL)ETHER, ... (8 entities in total)
• 機能のキーワード: clathrin heavy chain 1, endocytosis
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42452.63

構造登録者

Bulut, H.,Horatscheck, A.,Krauss, M.,Santos, K.F.,McCluskey, A.,Wahl, C.W.,Nazare, M.,Haucke, V. (登録日: 2024-05-28, 公開日: 2024-06-26, 最終更新日: 2025-05-14)

主引用文献

Horatscheck, A.,Krauss, M.,Bulut, H.,Chambon, V.,Zadah, M.S.,Dransart, E.,Peloza, K.,Santos, K.F.,Robertson, M.J.,Prichard, K.,Miksche, S.,Radetzki, S.,von Kries, J.P.,Wahl, M.C.,McCluskey, A.,Johannes, L.,Haucke, V.,Nazare, M.
Next-generation small molecule inhibitors of clathrin function acutely inhibit endocytosis.
Structure, 33:878-, 2025

PubMed Abstract: Clathrin-mediated endocytosis (CME) is the predominant endocytic pathway in eukaryotic cells and a major regulator of cell physiology as it facilitates the internalization of receptors, channels, and transporters and viral entry. The clathrin terminal domain acts as a central protein interaction hub within the endocytic protein network. Previously described inhibitors of CME display off-target activities that result in cytotoxicity, providing limitations to their use. We report the development and characterization of next-generation small molecule inhibitors of clathrin terminal domain function. These compounds termed Pitstop 2c and Pitstop 2d occupy the binding site within the clathrin terminal domain for endocytic protein ligands including epsin, resulting in potent inhibition of receptor-mediated endocytosis and reduced entry of vesicular stomatitis virus (VSV) with minimal cytotoxic side effects. Next-generation Pitstops thus provide an improved toolset to address clathrin function in cell physiology with potential applications as inhibitors of virus and pathogen entry.

PubMed: 40112806
DOI: 10.1016/j.str.2025.02.011

実験手法

X-RAY DIFFRACTION (1.4 Å)