View source for 4oq4


==Crystal Structure of E18A Human DJ-1==
<StructureSection load='4oq4' size='340' side='right'caption='[[4oq4]], [[Resolution|resolution]] 1.49&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4oq4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OQ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OQ4 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.49&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4oq4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oq4 OCA], [https://pdbe.org/4oq4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oq4 RCSB], [https://www.ebi.ac.uk/pdbsum/4oq4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oq4 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PARK7_HUMAN PARK7_HUMAN] Defects in PARK7 are the cause of Parkinson disease type 7 (PARK7) [MIM:[https://omim.org/entry/606324 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).<ref>PMID:12851414</ref> <ref>PMID:12446870</ref> <ref>PMID:14713311</ref> <ref>PMID:12953260</ref> <ref>PMID:15365989</ref> <ref>PMID:14607841</ref> <ref>PMID:15254937</ref> <ref>PMID:17846173</ref> 
== Function ==
[https://www.uniprot.org/uniprot/PARK7_HUMAN 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.<ref>PMID:9070310</ref> <ref>PMID:11477070</ref> <ref>PMID:12612053</ref> <ref>PMID:14749723</ref> <ref>PMID:15502874</ref> <ref>PMID:15976810</ref> <ref>PMID:16390825</ref> <ref>PMID:17015834</ref> <ref>PMID:18626009</ref> <ref>PMID:18711745</ref> <ref>PMID:20304780</ref> <ref>PMID:21097510</ref> <ref>PMID:12939276</ref> <ref>PMID:15181200</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The oxidation of a key cysteine residue (Cys106) in the parkinsonism-associated protein DJ-1 regulates its ability to protect against oxidative stress and mitochondrial damage. Cys106 interacts with a neighboring protonated Glu18 residue, stabilizing the Cys106-SO2 - (sulfinic acid) form of DJ-1. To study this important post-translational modification, we previously designed several Glu18 mutations (E18N, E18D, E18Q) that alter the oxidative propensity of Cys106. However, recent results suggest these Glu18 mutations cause loss of DJ-1 dimerization, which would severely compromise the protein's function. The purpose of this study was to conclusively determine the oligomerization state of these mutants using X-ray crystallography, NMR spectroscopy, thermal stability analysis, CD spectroscopy, sedimentation equilibrium ultracentrifugation, and crosslinking. We found that all of the Glu18 DJ-1 mutants were dimeric. Thiol crosslinking indicates that these mutant dimers are more flexible than the wild-type protein and can form multiple crosslinked dimeric species due to the transient exposure of cysteine residues that are inaccessible in the wild-type protein. The enhanced flexibility of Glu18 DJ-1 mutants provides a parsimonious explanation for their lower observed crosslinking efficiency in cells. In addition, thiol crosslinkers may have an underappreciated value as qualitative probes of protein conformational flexibility. This article is protected by copyright. All rights reserved.

Use of cysteine-reactive crosslinkers to probe conformational flexibility of human DJ-1 demonstrates that Glu18 mutations are dimers.,Prahlad J, Hauser DN, Milkovic NM, Cookson MR, Wilson MA J Neurochem. 2014 May 15. doi: 10.1111/jnc.12763. PMID:24832775<ref>PMID:24832775</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4oq4" style="background-color:#fffaf0;"></div>

==See Also==
*[[Protein DJ-1|Protein DJ-1]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cookson MR]]
[[Category: Hauser DN]]
[[Category: Milkovic NM]]
[[Category: Prahlad J]]
[[Category: Wilson MA]]