6E5Z
Crystal structure of human DJ-1 with a natural modification on Cys-106
Summary for 6E5Z
| Entry DOI | 10.2210/pdb6e5z/pdb |
| Related | 3CZA |
| Descriptor | Protein/nucleic acid deglycase DJ-1, CHLORIDE ION (3 entities in total) |
| Functional Keywords | the exact function of this protein is still unknown, hydrolase, unknown function |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 20174.12 |
| Authors | Shumilin, I.A.,Shumilina, S.V.,Minor, W. (deposition date: 2018-07-23, release date: 2018-08-01, Last modification date: 2023-10-11) |
| Primary citation | 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 Cited by 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: 30190129DOI: 10.1016/j.bbrc.2018.08.190 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.35 Å) |
Structure validation
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