6spa: Difference between revisions

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OCA

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-'''Unreleased structure'''
-The entry 6spa is ON HOLD
+==A4V MUTANT OF HUMAN SUPEROXIDE DISMUTASE 1 IN C2 SPACE GROUP==
+<StructureSection load='6spa' size='340' side='right'caption='[[6spa]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6spa]] is a 6 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=6SPA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SPA 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]] 1.65&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6spa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6spa OCA], [https://pdbe.org/6spa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6spa RCSB], [https://www.ebi.ac.uk/pdbsum/6spa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6spa ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/SODC_HUMAN SODC_HUMAN] Defects in SOD1 are the cause of amyotrophic lateral sclerosis type 1 (ALS1) [MIM:[https://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 ==
+[https://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 ==
+Mutations to the gene encoding superoxide dismutase-1 (SOD1) were the first genetic elements discovered that cause motor neuron disease (MND). These mutations result in compromised SOD1 dimer stability, with one of the severest and most common mutations Ala4Val (A4V) displaying a propensity to monomerise and aggregate leading to neuronal death. We show that the clinically used ebselen and related analogues promote thermal stability of A4V SOD1 when binding to Cys111 only. We have developed a A4V SOD1 differential scanning fluorescence-based assay on a C6S mutation background that is effective in assessing suitability of compounds. Crystallographic data show that the selenium atom of these compounds binds covalently to A4V SOD1 at Cys111 at the dimer interface, resulting in stabilisation. This together with chemical amenability for hit expansion of ebselen and its on-target SOD1 pharmacological chaperone activity holds remarkable promise for structure-based therapeutics for MND using ebselen as a template.
-Authors: Shahid, M., Chantadul, V., Amporndanai, K., Wright, G., Antonyuk, S., Hasnain, S.
+Ebselen as template for stabilization of A4V mutant dimer for motor neuron disease therapy.,Chantadul V, Wright GSA, Amporndanai K, Shahid M, Antonyuk SV, Washbourn G, Rogers M, Roberts N, Pye M, O'Neill PM, Hasnain SS Commun Biol. 2020 Mar 5;3(1):97. doi: 10.1038/s42003-020-0826-3. PMID:32139772<ref>PMID:32139772</ref>
-Description: A4V MUTANT OF HUMAN SUPEROXIDE DISMUTASE 1 IN C2 SPACE GROUP
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Antonyuk, S]]
+<div class="pdbe-citations 6spa" style="background-color:#fffaf0;"></div>
-[[Category: Hasnain, S]]
-[[Category: Shahid, M]]
+==See Also==
-[[Category: Amporndanai, K]]
+*[[Superoxide dismutase 3D structures|Superoxide dismutase 3D structures]]
-[[Category: Chantadul, V]]
+== References ==
-[[Category: Wright, G]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Amporndanai K]]
+[[Category: Antonyuk S]]
+[[Category: Chantadul V]]
+[[Category: Hasnain S]]
+[[Category: Shahid M]]
+[[Category: Wright G]]