3SF8: Structural Insights Into Thiol Stabilization Of Dj-1

Although the precise biochemical function of DJ-1 remains unclear, it has been found to exert cytoprotective activity against oxidative stress. Cys106 is central to this function since it has a distinctly low pK(a) rendering it extremely susceptible for oxidation. This characteristic, however, also poses a severe hindrance to obtain reduced DJ-1 for in vitro investigation. We have developed an approach to produce recombinant human DJ-1 in its reduced form as a bona fide basis for exploring the redox capacities of the protein. We solved the crystal structure of this DJ-1 at 1.56A resolution, allowing us to capture Cys106 in the reduced state for the first time. The dimeric structure reveals one molecule of DJ-1 in its reduced state while the other exhibits the characteristics of a mono-oxygenated cysteine. Comparison with previous structures indicates the absence of redox dependent global conformational changes in DJ-1. The capture of reduced Cys106 is facilitated by stabilization within the putative active site achieved through a glutamate side chain. This side chain is provided by a crystallographic neighbor as part of a 'Leu-Glu' motif, which was added to the C-terminus of DJ-1. In the structure this motif binds DJ-1 in close proximity to Cys106 through extended hydrophilic and hydrophobic interactions depicting a distinct binding pocket, which can serve as a basis for compound development targeting DJ-1.
PDB ID: 3SF8Download
MMDB ID: 94059
PDB Deposition Date: 2011/6/13
Updated in MMDB: 2011/11
Experimental Method:
x-ray diffraction
Resolution: 1.56  Å
Source Organism:
Similar Structures:
Biological Unit for 3SF8: dimeric; determined by author and by software (PISA)
Molecular Components in 3SF8
Label Count Molecule
Proteins (2 molecules)
Protein Dj-1(Gene symbol: PARK7)
Molecule annotation
Protein Dj-1(Gene symbol: PARK7)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB