5BOU

Yeast 20S proteasome in complex with a beta1 / beta2 specific non-peptidic sulfonamide Ligand

5BOU の概要

• エントリーDOI: 10.2210/pdb5bou/pdb
• 関連するPDBエントリー: 1RYP
• 分子名称: Proteasome subunit alpha type-2, Proteasome subunit beta type-4, Proteasome subunit beta type-5, ... (18 entities in total)
• 機能のキーワード: hydrolase-hydrolase inhibitor complex, proteasome, non-covalent ligand, binding analysis, hydrolase/hydrolase inhibitor
• 由来する生物種: Saccharomyces cerevisiae S288c (Baker's yeast); 詳細
• 細胞内の位置: Cytoplasm: P23639 P22141 P30656 P23724 P30657 P38624 P23638 P40303 P32379 P40302 P21242 P21243 P25043 P25451
• タンパク質・核酸の鎖数: 28
• 化学式量合計: 732295.20

構造登録者

Beck, P.,Groll, M. (登録日: 2015-05-27, 公開日: 2015-08-19, 最終更新日: 2024-01-10)

主引用文献

Beck, P.,Reboud-Ravaux, M.,Groll, M.
Identification of a beta 1/ beta 2-Specific Sulfonamide Proteasome Ligand by Crystallographic Screening.
Angew.Chem.Int.Ed.Engl., 54:11275-11278, 2015

PubMed Abstract: The proteasome represents a validated drug target for the treatment of cancer, however, new types of inhibitors are required to tackle the development of resistant tumors. Current fluorescence-based screening methods suffer from low sensitivity and are limited to the detection of ligands with conventional binding profiles. In response to these drawbacks, a crystallographic screening procedure for the discovery of agents with a novel mode of action was utilized. The optimized workflow was applied to the screening of a focused set of compounds, resulting in the discovery of a β1/β2-specific sulfonamide derivative that noncovalently binds between subunits β1 and β2. The binding pocket displays significant differences in size and polarity between the immuno- and constitutive proteasome. The identified ligand thus provides valuable insights for the future structure-based design of subtype-specific proteasome inhibitors.

PubMed: 26242779
DOI: 10.1002/anie.201505054

実験手法

X-RAY DIFFRACTION (2.6 Å)