4U54

IMPORTIN-ALPHA MINOR NLS SITE INHIBITOR

4U54 の概要

• エントリーDOI: 10.2210/pdb4u54/pdb
• 分子名称: Importin subunit alpha-1, N-methyl-1-[3-(pyridin-3-yl)phenyl]methanamine (3 entities in total)
• 機能のキーワード: tpx2 inhibitor, transport protein
• 由来する生物種: Mus musculus (Mouse)
• 細胞内の位置: Cytoplasm : P52293
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 46283.07

構造登録者

Stewart, M.,Valkov, E.,Holvey, R.S. (登録日: 2014-07-24, 公開日: 2015-05-13, 最終更新日: 2024-05-08)

主引用文献

Holvey, R.S.,Valkov, E.,Neal, D.,Stewart, M.,Abell, C.
Selective Targeting of the TPX2 Site of Importin-alpha Using Fragment-Based Ligand Design.
Chemmedchem, 10:1232-1239, 2015

PubMed Abstract: Protein-protein interactions are difficult therapeutic targets, and inhibiting pathologically relevant interactions without disrupting other essential ones presents an additional challenge. Herein we report how this might be achieved for the potential anticancer target, the TPX2-importin-α interaction. Importin-α is a nuclear transport protein that regulates the spindle assembly protein TPX2. It has two binding sites--major and minor-to which partners bind. Most nuclear transport cargoes use the major site, whereas TPX2 binds principally to the minor site. Fragment-based approaches were used to identify small molecules that bind importin-α, and crystallographic studies identified a lead series that was observed to bind specifically to the minor site, representing the first ligands specific for this site. Structure-guided synthesis informed the elaboration of these fragments to explore the source of ligand selectivity between the minor and major sites. These ligands are starting points for the development of inhibitors of this protein-protein interaction.

PubMed: 25899172
DOI: 10.1002/cmdc.201500014

実験手法

X-RAY DIFFRACTION (2.41 Å)