6E5Z

Crystal structure of human DJ-1 with a natural modification on Cys-106

6E5Z の概要

• エントリーDOI: 10.2210/pdb6e5z/pdb
• 関連するPDBエントリー: 3CZA
• 分子名称: Protein/nucleic acid deglycase DJ-1, CHLORIDE ION (3 entities in total)
• 機能のキーワード: the exact function of this protein is still unknown, hydrolase, unknown function
• 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: 20174.12

構造登録者

Shumilin, I.A.,Shumilina, S.V.,Minor, W. (登録日: 2018-07-23, 公開日: 2018-08-01, 最終更新日: 2023-10-11)

主引用文献

Mussakhmetov, A.,Shumilin, I.A.,Nugmanova, R.,Shabalin, I.G.,Baizhumanov, T.,Toibazar, D.,Khassenov, B.,Minor, W.,Utepbergenov, D.
A transient post-translational modification of active site cysteine alters binding properties of the parkinsonism protein DJ-1.
Biochem. Biophys. Res. Commun., 504:328-333, 2018

PubMed Abstract: Mutations in the human protein DJ-1 cause early onset of Parkinson's disease. A reactive cysteine residue (Cys) of DJ-1 is crucial for its protective function, although the underlying mechanisms are unclear. Here we show that a fraction of bacterially expressed polyhistidine-tagged human DJ-1 could not be eluted from a Ni-nitrilotriacetate (Ni-NTA) column with 150 mM imidazole. This unusually tight binding was accompanied by the appearance of blue violet color on the Ni-NTA column. We demonstrate by X-ray crystallography that Cys is carboxymethylated in a fraction of DJ-1 tightly bound to Ni-NTA and that the replacement of Cys by serine abrogates the tight binding and the appearance of blue violet color. However, carboxymethylation of purified DJ-1 is insufficient to confer the tight binding to Ni-NTA. Moreover, when eluted protein was re-applied to the Ni-NTA column, no tight binding was observed, indicating that the formation of high affinity complex with Ni-NTA depends on a transient modification of Cys that transforms into a Cys-carboxymethyl adduct upon elution from Ni-NTA. We conclude that an unknown metabolite reacts with Cys of DJ-1 to result in a transient post-translational modification. This modification is distinct from simple oxidation to sulfinic or sulfenic acids and confers altered binding properties to DJ-1 suggesting that it could serve as a signal for sensing oxidant stress.

PubMed: 30190129
DOI: 10.1016/j.bbrc.2018.08.190

実験手法

X-RAY DIFFRACTION (1.35 Å)