5k02: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older editNewer edit →
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
m Protected "5k02" [edit=sysop:move=sysop]
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
No edit summary
Line 1: Line 1:
'''Unreleased structure'''


The entry 5k02 is ON HOLD
==Structure of human SOD1 with T2D mutation==
<StructureSection load='5k02' size='340' side='right' caption='[[5k02]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5k02]] is a 24 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K02 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K02 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Superoxide_dismutase Superoxide dismutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.15.1.1 1.15.1.1] </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=5k02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k02 OCA], [http://pdbe.org/5k02 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k02 RCSB], [http://www.ebi.ac.uk/pdbsum/5k02 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k02 ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/SODC_HUMAN SODC_HUMAN]] Defects in SOD1 are the cause of amyotrophic lateral sclerosis type 1 (ALS1) [MIM:[http://omim.org/entry/105400 105400]]. ALS1 is a familial form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of cases leading to familial forms.<ref>PMID:12963370</ref> <ref>PMID:19741096</ref> <ref>PMID:8528216</ref> <ref>PMID:8682505</ref> <ref>PMID:9541385</ref> <ref>PMID:12754496</ref> <ref>PMID:15056757</ref> <ref>PMID:18378676</ref> [:]<ref>PMID:8446170</ref> <ref>PMID:8351519</ref> <ref>PMID:8179602</ref> <ref>PMID:7980516</ref> <ref>PMID:8069312</ref> <ref>PMID:7951252</ref> <ref>PMID:7881433</ref> <ref>PMID:7836951</ref> <ref>PMID:7997024</ref> <ref>PMID:7870076</ref> <ref>PMID:7887412</ref> <ref>PMID:7795609</ref> <ref>PMID:7655468</ref> <ref>PMID:7655469</ref> <ref>PMID:7655471</ref> <ref>PMID:7700376</ref> <ref>PMID:7647793</ref> <ref>PMID:7501156</ref> <ref>PMID:7496169</ref> <ref>PMID:8938700</ref> <ref>PMID:8907321</ref> <ref>PMID:8990014</ref> <ref>PMID:9101297</ref> <ref>PMID:9455977</ref> <ref>PMID:10732812</ref> <ref>PMID:9131652</ref> <ref>PMID:10400992</ref> <ref>PMID:10430435</ref> <ref>PMID:11535232</ref> <ref>PMID:11369193</ref> <ref>PMID:12402272</ref> <ref>PMID:12145308</ref> <ref>PMID:14506936</ref> <ref>PMID:18552350</ref> <ref>PMID:18301754</ref> <ref>PMID:21247266</ref> <ref>PMID:21220647</ref> 
== Function ==
[[http://www.uniprot.org/uniprot/SODC_HUMAN SODC_HUMAN]] Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The majority of amyotrophic lateral sclerosis (ALS)-related mutations in the enzyme Cu,Zn superoxide dismutase (SOD1), as well as a post-translational modification, glutathionylation, destabilize the protein and lead to a misfolded oligomer that is toxic to motor neurons. The biophysical role of another physiological SOD1 modification, T2-phosphorylation, has remained a mystery. Here, we find that a phosphomimetic mutation, T2D, thermodynamically stabilizes SOD1 even in the context of a strongly SOD1-destabilizing mutation, A4V, one of the most prevalent and aggressive ALS-associated mutations in North America. This stabilization protects against formation of toxic SOD oligomers and positively impacts motor neuron survival in cellular assays. We solve the crystal structure of T2D-SOD1 and explain its stabilization effect using discrete molecular dynamics (DMD) simulations. These findings imply that T2-phosphorylation may be a plausible innate cellular protection response against SOD1-induced cytotoxicity, and stabilizing the SOD1 native conformation might offer us viable pharmaceutical strategies against currently incurable ALS.


Authors:  
A Phosphomimetic Mutation Stabilizes SOD1 and Rescues Cell Viability in the Context of an ALS-Associated Mutation.,Fay JM, Zhu C, Proctor EA, Tao Y, Cui W, Ke H, Dokholyan NV Structure. 2016 Nov 1;24(11):1898-1906. doi: 10.1016/j.str.2016.08.011. Epub 2016, Sep 22. PMID:27667694<ref>PMID:27667694</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 5k02" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Superoxide dismutase]]
[[Category: Cui, W]]
[[Category: Dokholyan, N V]]
[[Category: Fay, J M]]
[[Category: Ke, H]]
[[Category: Zhu, C]]
[[Category: Oxidoreductase]]
[[Category: Phosphomimetic mutation]]
[[Category: Sod1]]
Retrieved from "https://proteopedia.org/5k02"