3sf8

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
{{STRUCTURE_3sf8| PDB=3sf8 | SCENE= }}
+
==Structural insights into thiol stabilization of DJ-1==
-
===Structural insights into thiol stabilization of DJ-1===
+
<StructureSection load='3sf8' size='340' side='right' caption='[[3sf8]], [[Resolution|resolution]] 1.56&Aring;' scene=''>
-
{{ABSTRACT_PUBMED_21893204}}
+
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[3sf8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SF8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SF8 FirstGlance]. <br>
 +
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></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 Homo sapiens])</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=3sf8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sf8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sf8 RCSB], [http://www.ebi.ac.uk/pdbsum/3sf8 PDBsum]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[[http://www.uniprot.org/uniprot/PARK7_HUMAN PARK7_HUMAN]] Defects in PARK7 are the cause of Parkinson disease type 7 (PARK7) [MIM:[http://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 ==
 +
[[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 ==
 +
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.
-
==Disease==
+
Identification of an artificial peptide motif that binds and stabilizes reduced human DJ-1.,Premkumar L, Dobaczewska MK, Riedl SJ J Struct Biol. 2011 Aug 27. PMID:21893204<ref>PMID:21893204</ref>
-
[[http://www.uniprot.org/uniprot/PARK7_HUMAN PARK7_HUMAN]] Defects in PARK7 are the cause of Parkinson disease type 7 (PARK7) [MIM:[http://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==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[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>
-
 
+
== References ==
-
==About this Structure==
+
<references/>
-
[[3sf8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SF8 OCA].
+
__TOC__
-
 
+
</StructureSection>
-
==Reference==
+
-
<ref group="xtra">PMID:021893204</ref><references group="xtra"/><references/>
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Dobaczewska, M K.]]
+
[[Category: Dobaczewska, M K]]
-
[[Category: Premkumar, L.]]
+
[[Category: Premkumar, L]]
-
[[Category: Riedl, S J.]]
+
[[Category: Riedl, S J]]
[[Category: Class i glutamine amidotransferase family]]
[[Category: Class i glutamine amidotransferase family]]
[[Category: Cysteine oxidation]]
[[Category: Cysteine oxidation]]

Revision as of 07:31, 21 December 2014

Structural insights into thiol stabilization of DJ-1

3sf8, resolution 1.56Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3sf8"
Personal tools