6E4L

The structure of the N-terminal domain of human clathrin heavy chain 1 (nTD) in complex with ES9

6E4L の概要

• エントリーDOI: 10.2210/pdb6e4l/pdb
• 分子名称: Clathrin heavy chain 1, DIMETHYL SULFOXIDE, GLYCEROL, ... (7 entities in total)
• 機能のキーワード: clathrin-mediated endocytosis (cme), clathrin n-terminal domain (ntd), chemical inhibition, 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: 41973.87

構造登録者

Dejonghe, W.,Sharma, I.,Denoo, B.,Munck, S.D.,Bulut, H.,Mylle, E.,Vasileva, M.,Lu, Q.,Savatin, D.V.,Mishev, K.,Nerinckx, W.,Staes, A.,Drozdzecki, A.,Audenaert, D.,Madder, A.,Friml, J.,Damme, D.V.,Gevaert, K.,Haucke, V.,Savvides, S.,Winne, J.,Russinova, E. (登録日: 2018-07-17, 公開日: 2019-04-24, 最終更新日: 2023-10-11)

主引用文献

Dejonghe, W.,Sharma, I.,Denoo, B.,De Munck, S.,Lu, Q.,Mishev, K.,Bulut, H.,Mylle, E.,De Rycke, R.,Vasileva, M.,Savatin, D.V.,Nerinckx, W.,Staes, A.,Drozdzecki, A.,Audenaert, D.,Yperman, K.,Madder, A.,Friml, J.,Van Damme, D.,Gevaert, K.,Haucke, V.,Savvides, S.N.,Winne, J.,Russinova, E.
Disruption of endocytosis through chemical inhibition of clathrin heavy chain function.
Nat.Chem.Biol., 15:641-649, 2019

PubMed Abstract: Clathrin-mediated endocytosis (CME) is a highly conserved and essential cellular process in eukaryotic cells, but its dynamic and vital nature makes it challenging to study using classical genetics tools. In contrast, although small molecules can acutely and reversibly perturb CME, the few chemical CME inhibitors that have been applied to plants are either ineffective or show undesirable side effects. Here, we identify the previously described endosidin9 (ES9) as an inhibitor of clathrin heavy chain (CHC) function in both Arabidopsis and human cells through affinity-based target isolation, in vitro binding studies and X-ray crystallography. Moreover, we present a chemically improved ES9 analog, ES9-17, which lacks the undesirable side effects of ES9 while retaining the ability to target CHC. ES9 and ES9-17 have expanded the chemical toolbox used to probe CHC function, and present chemical scaffolds for further design of more specific and potent CHC inhibitors across different systems.

PubMed: 31011214
DOI: 10.1038/s41589-019-0262-1

実験手法

X-RAY DIFFRACTION (1.6 Å)