3OEV

Structure of yeast 20S open-gate proteasome with Compound 25

3OEV の概要

• エントリーDOI: 10.2210/pdb3oev/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000959
• 分子名称: Proteasome component Y7, Proteasome component C11, Proteasome component PRE2, ... (17 entities in total)
• 機能のキーワード: 20s proteasome, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 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: 707767.21

構造登録者

Sintchak, M.D. (登録日: 2010-08-13, 公開日: 2011-07-20, 最終更新日: 2024-02-21)

主引用文献

Blackburn, C.,Barrett, C.,Blank, J.L.,Bruzzese, F.J.,Bump, N.,Dick, L.R.,Fleming, P.,Garcia, K.,Hales, P.,Hu, Z.,Jones, M.,Liu, J.X.,Sappal, D.S.,Sintchak, M.D.,Tsu, C.,Gigstad, K.M.
Optimization of a series of dipeptides with a P3 threonine residue as non-covalent inhibitors of the chymotrypsin-like activity of the human 20S proteasome.
Bioorg.Med.Chem.Lett., 20:6581-6586, 2010

PubMed Abstract: Starting from a tripeptide screening hit, a series of dipeptide inhibitors of the proteasome with Thr as the P3 residue has been optimized with the aid of crystal structures in complex with the β-5/6 active site of y20S. Derivative 25, (β5 IC(50)=7.4 nM) inhibits only the chymotryptic activity of the proteasome, shows cellular activity against targets in the UPS, and inhibits proliferation.

PubMed: 20875739
DOI: 10.1016/j.bmcl.2010.09.032

実験手法

X-RAY DIFFRACTION (2.85 Å)