7R2G

USP15 D1D2 in catalytically-competent state bound to mitoxantrone stack (isoform 2)

7R2G の概要

• エントリーDOI: 10.2210/pdb7r2g/pdb
• 分子名称: Ubiquitin carboxyl-terminal hydrolase 15, ZINC ION, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: cysteine protease, hydrolase
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 88624.68

構造登録者

Priyanka, A.,Sixma, T.K. (登録日: 2022-02-04, 公開日: 2022-06-08, 最終更新日: 2024-01-31)

主引用文献

Priyanka, A.,Tisi, D.,Sixma, T.K.
Mitoxantrone stacking does not define the active or inactive state of USP15 catalytic domain.
J.Struct.Biol., 214:107862-107862, 2022

PubMed Abstract: Ubiquitin specific protease USP15 is a deubiquitinating enzyme reported to regulate several biological and cellular processes, including TGF-β signaling, regulation of immune response, neuro-inflammation and mRNA splicing. Here we study the USP15 D1D2 catalytic domain and present the crystal structure in its catalytically-competent conformation. We compare this apo-structure to a previous misaligned state in the same crystal lattice. In both structures, mitoxantrone, an FDA approved antineoplastic drug and a weak inhibitor of USP15 is bound, indicating that it is not responsible for inducing a switch in the conformation of active site cysteine in the USP15 D1D2 structure. Instead, mitoxantrone contributes to crystal packing, by forming a stack of 12 mitoxantrone molecules. We believe this reflects how mitoxantrone can be responsible for e.g. nuclear condensate partitioning. We conclude that USP15 can switch between active and inactive states in the absence of ubiquitin, and that this is independent of mitoxantrone binding. These insights can be important for future drug discovery targeting USP15.

PubMed: 35605756
DOI: 10.1016/j.jsb.2022.107862

実験手法

X-RAY DIFFRACTION (1.98 Å)