4MDK

Cdc34-ubiquitin-CC0651 complex

4MDK の概要

• エントリーDOI: 10.2210/pdb4mdk/pdb
• 分子名称: Ubiquitin-conjugating enzyme E2 R1, Ubiquitin, 4,5-dideoxy-5-(3',5'-dichlorobiphenyl-4-yl)-4-[(methoxyacetyl)amino]-L-arabinonic acid, ... (4 entities in total)
• 機能のキーワード: ubiquitin conjugating enzyme domain, e2 ligase inhibitor, ligase-ligase inhibitor complex, ligase/ligase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: P49427; Ubiquitin: Cytoplasm (By similarity): P0CG48
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 119342.64

構造登録者

Ceccarelli, D.F.,Orlicky, S.,Tyers, M.,Sicheri, F. (登録日: 2013-08-22, 公開日: 2013-12-11, 最終更新日: 2023-09-20)

主引用文献

Huang, H.,Ceccarelli, D.F.,Orlicky, S.,St-Cyr, D.J.,Ziemba, A.,Garg, P.,Plamondon, S.,Auer, M.,Sidhu, S.,Marinier, A.,Kleiger, G.,Tyers, M.,Sicheri, F.
E2 enzyme inhibition by stabilization of a low-affinity interface with ubiquitin.
Nat.Chem.Biol., 10:156-163, 2014

PubMed Abstract: Weak protein interactions between ubiquitin and the ubiquitin-proteasome system (UPS) enzymes that mediate its covalent attachment to substrates serve to position ubiquitin for optimal catalytic transfer. We show that a small-molecule inhibitor of the E2 ubiquitin-conjugating enzyme Cdc34A, called CC0651, acts by trapping a weak interaction between ubiquitin and the E2 donor ubiquitin-binding site. A structure of the ternary CC0651-Cdc34A-ubiquitin complex reveals that the inhibitor engages a composite binding pocket formed from Cdc34A and ubiquitin. CC0651 also suppresses the spontaneous hydrolysis rate of the Cdc34A-ubiquitin thioester without decreasing the interaction between Cdc34A and the RING domain subunit of the E3 enzyme. Stabilization of the numerous other weak interactions between ubiquitin and UPS enzymes by small molecules may be a feasible strategy to selectively inhibit different UPS activities.

PubMed: 24316736
DOI: 10.1038/nchembio.1412

実験手法

X-RAY DIFFRACTION (2.6095 Å)