6m8z
From Proteopedia
(Difference between revisions)
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<StructureSection load='6m8z' size='340' side='right' caption='[[6m8z]], [[Resolution|resolution]] 1.83Å' scene=''> | <StructureSection load='6m8z' size='340' side='right' caption='[[6m8z]], [[Resolution|resolution]] 1.83Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6m8z]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M8Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6M8Z FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6m8z]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M8Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6M8Z FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6e5z|6e5z]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6e5z|6e5z]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PARK7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6m8z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m8z OCA], [http://pdbe.org/6m8z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6m8z RCSB], [http://www.ebi.ac.uk/pdbsum/6m8z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6m8z ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6m8z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m8z OCA], [http://pdbe.org/6m8z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6m8z RCSB], [http://www.ebi.ac.uk/pdbsum/6m8z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6m8z ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
[[http://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> | [[http://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 == | ||
| + | Mutations in the human protein DJ-1 cause early onset of Parkinson's disease. A reactive cysteine residue (Cys(106)) 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 150mM 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(106) is carboxymethylated in a fraction of DJ-1 tightly bound to Ni-NTA and that the replacement of Cys(106) 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(106) that transforms into a Cys(106)-carboxymethyl adduct upon elution from Ni-NTA. We conclude that an unknown metabolite reacts with Cys(106) 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. | ||
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| + | A transient post-translational modification of active site cysteine alters binding properties of the parkinsonism protein DJ-1.,Mussakhmetov A, Shumilin IA, Nugmanova R, Shabalin IG, Baizhumanov T, Toibazar D, Khassenov B, Minor W, Utepbergenov D Biochem Biophys Res Commun. 2018 Sep 26;504(1):328-333. doi:, 10.1016/j.bbrc.2018.08.190. Epub 2018 Sep 4. PMID:30190129<ref>PMID:30190129</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6m8z" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Minor, W]] | [[Category: Minor, W]] | ||
[[Category: Shabalin, I G]] | [[Category: Shabalin, I G]] | ||
Revision as of 20:24, 19 September 2018
Crystal structure of human DJ-1 without a modification on Cys-106
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