6ZQH

Yeast Uba1 in complex with ubiquitin

6ZQH の概要

• エントリーDOI: 10.2210/pdb6zqh/pdb
• 関連するPDBエントリー: 3CMM
• 分子名称: Ubiquitin-activating enzyme E1 1, Ubiquitin-40S ribosomal protein S31, BETA-MERCAPTOETHANOL, ... (6 entities in total)
• 機能のキーワード: ubiquitin, e1, ligase
• 由来する生物種: Saccharomyces cerevisiae (Baker's yeast); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 246800.36

構造登録者

Misra, M.,Schindelin, H. (登録日: 2020-07-09, 公開日: 2020-11-04, 最終更新日: 2024-01-31)

主引用文献

Kim, R.Q.,Misra, M.,Gonzalez, A.,Tomaskovic, I.,Shin, D.,Schindelin, H.,Filippov, D.V.,Ovaa, H.,Dikic, I.,van der Heden van Noort, G.J.
Development of ADPribosyl Ubiquitin Analogues to Study Enzymes Involved in Legionella Infection.
Chemistry, 27:2506-2512, 2021

PubMed Abstract: Legionnaires' disease is caused by infection with the intracellularly replicating Gram-negative bacterium Legionella pneumophila. This pathogen uses an unconventional way of ubiquitinating host proteins by generating a phosphoribosyl linkage between substrate proteins and ubiquitin by making use of an ADPribosylated ubiquitin (Ub ) intermediate. The family of SidE effector enzymes that catalyze this reaction is counteracted by Legionella hydrolases, which are called Dups. This unusual ubiquitination process is important for Legionella proliferation and understanding these processes on a molecular level might prove invaluable in finding new treatments. Herein, a modular approach is used for the synthesis of triazole-linked Ub , and analogues thereof, and their affinity towards the hydrolase DupA is determined and hydrolysis rates are compared to natively linked Ub . The inhibitory effects of modified Ub on the canonical eukaryotic E1-enzyme Uba1 are investigated and rationalized in the context of a high-resolution crystal structure reported herein. Finally, it is shown that synthetic Ub analogues can be used to effectively pull-down overexpressed DupA from cell lysate.

PubMed: 33075184
DOI: 10.1002/chem.202004590

実験手法

X-RAY DIFFRACTION (2.032 Å)