5LEY

Human 20S proteasome complex with Oprozomib at 1.9 Angstrom

5LEY の概要

• エントリーDOI: 10.2210/pdb5ley/pdb
• 分子名称: Proteasome subunit alpha type-2, Proteasome subunit beta type-2, Proteasome subunit beta type-5, ... (20 entities in total)
• 機能のキーワード: proteasome, multicatalytic proteinase, ntn-hydrolase, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm : P25787 P49721 P28074 P20618 P28070 P28072 P25789 O14818 P28066 P25786 P25788 P60900 Q99436 P49720
• タンパク質・核酸の鎖数: 30
• 化学式量合計: 724844.27

構造登録者

Schrader, J.,Henneberg, F.,Mata, R.,Tittmann, K.,Schneider, T.R.,Stark, H.,Bourenkov, G.,Chari, A. (登録日: 2016-06-30, 公開日: 2016-08-17, 最終更新日: 2024-01-10)

主引用文献

Schrader, J.,Henneberg, F.,Mata, R.A.,Tittmann, K.,Schneider, T.R.,Stark, H.,Bourenkov, G.,Chari, A.
The inhibition mechanism of human 20S proteasomes enables next-generation inhibitor design.
Science, 353:594-598, 2016

PubMed Abstract: The proteasome is a validated target for anticancer therapy, and proteasome inhibition is employed in the clinic for the treatment of tumors and hematological malignancies. Here, we describe crystal structures of the native human 20S proteasome and its complexes with inhibitors, which either are drugs approved for cancer treatment or are in clinical trials. The structure of the native human 20S proteasome was determined at an unprecedented resolution of 1.8 angstroms. Additionally, six inhibitor-proteasome complex structures were elucidated at resolutions between 1.9 and 2.1 angstroms. Collectively, the high-resolution structures provide new insights into the catalytic mechanisms of inhibition and necessitate a revised description of the proteasome active site. Knowledge about inhibition mechanisms provides insights into peptide hydrolysis and can guide strategies for the development of next-generation proteasome-based cancer therapeutics.

PubMed: 27493187
DOI: 10.1126/science.aaf8993

実験手法

X-RAY DIFFRACTION (1.9 Å)