3DY3

Crystal structure of yeast 20S proteasome in complex with the epimer form of spirolactacystin

3DY3 の概要

• エントリーDOI: 10.2210/pdb3dy3/pdb
• 関連するPDBエントリー: 1RYP 3DY4
• 分子名称: Proteasome component Y7, Proteasome component C11, Proteasome component PRE2, ... (16 entities in total)
• 機能のキーワード: proteasome, inhibitor, protein degradation, ubiquitin-proteasome-pathway, cytoplasm, hydrolase, nucleus, protease, threonine protease, ubl conjugation, phosphoprotein, zymogen
• 由来する生物種: Saccharomyces cerevisiae (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: 704668.73

構造登録者

Groll, M.,Balskus, E.,Jacobsen, E. (登録日: 2008-07-25, 公開日: 2008-11-04, 最終更新日: 2024-10-09)

主引用文献

Groll, M.,Balskus, E.P.,Jacobsen, E.N.
Structural analysis of spiro beta-lactone proteasome inhibitors.
J.Am.Chem.Soc., 130:14981-14983, 2008

PubMed Abstract: Spiro beta-lactone-based proteasome inhibitors were discovered in the context of an asymmetric catalytic total synthesis of the natural product (+)-lactacystin (1). Lactone 4 was found to be a potent inhibitor of the 26S proteasome, while its C-6 epimer (5) displayed weak activity. Crystallographic studies of the two analogues covalently bound to the 20S proteasome permitted characterization of the important stabilizing interactions between each inhibitor and the proteasome's key catalytic N-terminal threonine residue. This structural data support the hypothesis that the discrepancy in potency between 4 and 5 may be due to differences in the hydrolytic stabilities of the resulting acyl enzyme complexes.

PubMed: 18928262
DOI: 10.1021/ja806059t

実験手法

X-RAY DIFFRACTION (2.81 Å)