5L6H

Uba1 in complex with Ub-ABPA3 covalent adduct

「3CMM」から置き換えられました 「4NNJ」から置き換えられました

5L6H の概要

• エントリーDOI: 10.2210/pdb5l6h/pdb
• 分子名称: Ubiquitin-activating enzyme E1 1, Ubiquitin-40S ribosomal protein S31, SULFATE ION, ... (9 entities in total)
• 機能のキーワード: e1 enzyme, ubiquitin activation, uba1 inhibitor, adenosyl sulfamate, ligase
• 由来する生物種: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); 詳細
• 細胞内の位置: Cytoplasm: P22515; Ubiquitin: Cytoplasm . 40S ribosomal protein S31: Cytoplasm : P05759
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 256991.00

構造登録者

Misra, M.,Schindelin, H. (登録日: 2016-05-30, 公開日: 2017-06-14, 最終更新日: 2024-10-09)

主引用文献

Misra, M.,Kuhn, M.,Lobel, M.,An, H.,Statsyuk, A.V.,Sotriffer, C.,Schindelin, H.
Dissecting the Specificity of Adenosyl Sulfamate Inhibitors Targeting the Ubiquitin-Activating Enzyme.
Structure, 25:1120-1129.e3, 2017

PubMed Abstract: Targeting the activating enzymes (E1) of ubiquitin (Ub) and ubiquitin-like modifiers (Ubls) has emerged as a promising anti-cancer strategy, possibly overcoming the ineffectiveness of proteasome inhibitors against solid tumors. Here, we report crystal structures of the yeast ubiquitin E1 (Uba1) with three adenosyl sulfamate inhibitors exhibiting different E1 specificities, which are all covalently linked to ubiquitin. The structures illustrate how the chemically diverse inhibitors are accommodated within the adenylation active site. When compared with the previously reported structures of various E1 enzymes, our structures provide the basis of the preferences of these inhibitors for different Ub/Ubl-activating enzymes. In vitro inhibition assays and molecular dynamics simulations validated the specificities of the inhibitors as deduced from the structures. Taken together, the structures establish a framework for the development of additional compounds targeting E1 enzymes, which will display higher potency and selectivity.

PubMed: 28578874
DOI: 10.1016/j.str.2017.05.001

実験手法

X-RAY DIFFRACTION (2.3 Å)