4ogf

Crystal Structure of Human DJ-1 with glyoxylate as substrate analogCrystal Structure of Human DJ-1 with glyoxylate as substrate analog

Structural highlights 4ogf is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: Related: 4ofw, 4ogg Gene: PARK7 (HUMAN) Activity: D-lactate dehydratase, with EC number 4.2.1.130 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [PARK7_HUMAN] Defects in PARK7 are the cause of Parkinson disease type 7 (PARK7) [MIM:606324]. A neurodegenerative disorder characterized by resting tremor, postural tremor, bradykinesia, muscular rigidity, anxiety and psychotic episodes. PARK7 has onset before 40 years, slow progression and initial good response to levodopa. Some patients may show traits reminiscent of amyotrophic lateral sclerosis-parkinsonism/dementia complex (Guam disease). Function [PARK7_HUMAN] Protects cells against oxidative stress and cell death. Plays a role in regulating expression or stability of the mitochondrial uncoupling proteins SLC25A14 and SLC25A27 in dopaminergic neurons of the substantia nigra pars compacta and attenuates the oxidative stress induced by calcium entry into the neurons via L-type channels during pacemaking. Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death. May act as an atypical peroxiredoxin-like peroxidase that scavenges hydrogen peroxide. Following removal of a C-terminal peptide, displays protease activity and enhanced cytoprotective action against oxidative stress-induced apoptosis. Stabilizes NFE2L2 by preventing its association with KEAP1 and its subsequent ubiquitination. Binds to OTUD7B and inhibits its deubiquitinating activity. Enhances RELA nuclear translocation. Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress. Required for correct mitochondrial morphology and function and for autophagy of dysfunctional mitochondria. Regulates astrocyte inflammatory responses. Acts as a positive regulator of androgen receptor-dependent transcription. Prevents aggregation of SNCA. Plays a role in fertilization. Has no proteolytic activity. Has cell-growth promoting activity and transforming activity. May function as a redox-sensitive chaperone. Publication Abstract from PubMed DJ-1 family proteins have recently been characterized as novel glyoxalases, although their cofactor-free catalytic mechanisms are not fully understood. In this work, we obtained crystals of Arabidopsis thaliana DJ-1d (atDJ-1d) and Homo sapiens DJ-1 (hDJ-1) covalently bound to glyoxylate, an analog of methylglyoxal, forming a hemithioacetal that presumably mimics an intermediate structure in the catalysis from methylglyoxal to lactate. The level of deuteration in lactate formation supported the proton transfer mechanism in the enzyme reaction. Differences in the enantiomeric specificity of D/L-lactacte formation observed in the DJ-1 superfamily proteins were explained by the presence of a His residue in the active site with essential Cys and Glu residues. The model for the stereospecificity was further evaluated by a molecular modeling simulation with methylglyoxal hemithioacetal superimposed on the glyoxylate hemithioacetal. The DJ-1 glyoxalase provides a unique mechanism in understanding the His residue-involved stereospecificity. This article is protected by copyright. All rights reserved. Stereospecific mechanism of DJ-1 glyoxalases inferred from their hemithioacetal-containing crystal structures.,Choi D, Kim J, Ha S, Kwon K, Kim EH, Lee HY, Ryu KS, Park C FEBS J. 2014 Oct 4. doi: 10.1111/febs.13085. PMID:25283443 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 4ogf, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image