8CMS

OTUB2 in covalent complex with LN5P45

これはPDB形式変換不可エントリーです。

8CMS の概要

• エントリーDOI: 10.2210/pdb8cms/pdb
• 分子名称: Ubiquitin thioesterase OTUB2, (1~{S},2~{S})-~{N}'-ethanoyl-2-(3-methylphenyl)cyclopropane-1-carbohydrazide (3 entities in total)
• 機能のキーワード: chemical modification, ubiquitin, deubiquitinase, inhibitor, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27637.37

構造登録者

Gan, J.,de Vries, J. (登録日: 2023-02-21, 公開日: 2023-11-15, 最終更新日: 2024-11-06)

主引用文献

Gan, J.,de Vries, J.,Akkermans, J.J.L.L.,Mohammed, Y.,Tjokrodirijo, R.T.N.,de Ru, A.H.,Kim, R.Q.,Vargas, D.A.,Pol, V.,Fasan, R.,van Veelen, P.A.,Neefjes, J.,van Dam, H.,Ovaa, H.,Sapmaz, A.,Geurink, P.P.
Cellular Validation of a Chemically Improved Inhibitor Identifies Monoubiquitination on OTUB2.
Acs Chem.Biol., 18:2003-2013, 2023

PubMed Abstract: Ubiquitin thioesterase OTUB2, a cysteine protease from the ovarian tumor (OTU) deubiquitinase superfamily, is often overexpressed during tumor progression and metastasis. Development of OTUB2 inhibitors is therefore believed to be therapeutically important, yet potent and selective small-molecule inhibitors targeting OTUB2 are scarce. Here, we describe the development of an improved OTUB2 inhibitor, , comprising a chloroacethydrazide moiety that covalently reacts to the active-site cysteine residue. shows outstanding target engagement and proteome-wide selectivity in living cells. Importantly, as well as other OTUB2 inhibitors strongly induce monoubiquitination of OTUB2 on lysine 31. We present a route to future OTUB2-related therapeutics and have shown that the OTUB2 inhibitor developed in this study can help to uncover new aspects of the related biology and open new questions regarding the understanding of OTUB2 regulation at the post-translational modification level.

PubMed: 37642399
DOI: 10.1021/acschembio.3c00227

実験手法

X-RAY DIFFRACTION (1.77 Å)