3ZJF

A20 OTU domain with irreversibly oxidised Cys103 from 270 min H2O2 soak.

3ZJF の概要

• エントリーDOI: 10.2210/pdb3zjf/pdb
• 関連するPDBエントリー: 3ZJD 3ZJE 3ZJG
• 分子名称: A20P50, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: hydrolase, ubiquitin, deubiquitinating enzyme, reversible oxidation, sulphenic acid, cys protease
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Cytoplasm. A20p50: Cytoplasm: P21580 P21580
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 86417.91

構造登録者

Kulathu, Y.,Garcia, F.J.,Mevissen, T.E.T.,Busch, M.,Arnaudo, N.,Carroll, K.S.,Barford, D.,Komander, D. (登録日: 2013-01-17, 公開日: 2013-03-06, 最終更新日: 2023-12-20)

主引用文献

Kulathu, Y.,Garcia, F.J.,Mevissen, T.E.T.,Busch, M.,Arnaudo, N.,Carroll, K.S.,Barford, D.,Komander, D.
Regulation of A20 and Other Otu Deubiquitinases by Reversible Oxidation
Nat.Commun., 4:1569-, 2013

PubMed Abstract: Protein ubiquitination is a highly versatile post-translational modification that regulates as diverse processes as protein degradation and kinase activation. Deubiquitinases hydrolyse ubiquitin modifications from proteins and are hence key regulators of the ubiquitin system. Ovarian tumour deubiquitinases comprise a family of fourteen human enzymes, many of which regulate cellular signalling pathways. Ovarian tumour deubiquitinases are cysteine proteases that cleave polyubiquitin chains in vitro and in cells, but little is currently known about their regulation. Here we show that ovarian tumour deubiquitinases are susceptible to reversible oxidation of the catalytic cysteine residue. High-resolution crystal structures of the catalytic domain of A20 in four different oxidation states reveal that the reversible form of A20 oxidation is a cysteine sulphenic acid intermediate, which is stabilised by the architecture of the catalytic centre. Using chemical tools to detect sulphenic acid intermediates, we show that many ovarian tumour deubiquitinases undergo reversible oxidation upon treatment with H2O2, revealing a new mechanism to regulate deubiquitinase activity.

PubMed: 23463012
DOI: 10.1038/NCOMMS2567

実験手法

X-RAY DIFFRACTION (2.2 Å)