4ge0

Schizosaccharomyces pombe DJ-1 T114P mutantSchizosaccharomyces pombe DJ-1 T114P mutant

Structural highlights 4ge0 is a 4 chain structure with sequence from Schizosaccharomyces pombe. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.45Å Ligands: , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DJ1_SCHPO Catalyzes the conversion of methylglyoxal (MG) to D-lactate in a single glutathione (GSH)-independent step (PubMed:24758716). May play a role in detoxifying endogenously produced glyoxals. Involved in protection against reactive oxygen species (ROS) (By similarity).[UniProtKB:Q04432] Publication Abstract from PubMed Cysteine residues with depressed pK(a) values are critical for the functions of many proteins. Several types of interactions can stabilize cysteine thiolate anions, including hydrogen bonds between thiol(ate)s and nearby residues as well as electrostatic interactions involving charged residues or dipoles. Dipolar stabilization of thiolates by peptide groups has been suggested to play a particularly important role near the N-termini of alpha-helices. Using a combination of X-ray crystallography, site-directed mutagenesis, and spectroscopic methods, we show that the reactive cysteine residue (Cys111) in Schizosaccharomyces pombe DJ-1 experiences a 0.6 unit depression of its thiol pK(a) as a consequence of a hydrogen bond donated by a threonine sidechain (Thr114) to a nearby peptide carbonyl oxygen at the N-terminus of an alpha-helix. This extended hydrogen bonded interaction is consistent with a sum of dipoles model whereby the distal hydrogen bond polarizes and strengthens the direct hydrogen bond between the proximal amide hydrogen and the cysteine thiol(ate). Therefore, our results suggest that the local dipolar enhancement of hydrogen bonds can appreciably stabilize cysteine thiolate formation. However, the substitution of a valine residue with a proline at the i+3 position has only a minor effect (0.3 units) on the pK(a) of Cys111. As proline has a reduced peptide dipole moment, this small effect suggests that a more extended helix macrodipolar effect does not play a major role in this system. (c) 2012 The Authors Journal compilation (c) 2012 FEBS. Influence of Peptide Dipoles and Hydrogen Bonds on Reactive Cysteine pK(a) Values in Fission Yeast DJ-1.,Madzelan P, Labunksa T, Wilson MA FEBS J. 2012 Sep 12. doi: 10.1111/febs.12004. PMID:22971103 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 4ge0, resolution 1.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image