2nnx: Difference between revisions

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-[[Image:2nnx.png|left|200px]]
-{{STRUCTURE_2nnx|  PDB=2nnx  |  SCENE=  }}
+==Crystal Structure of the H46R, H48Q double mutant of human [Cu-Zn] Superoxide Dismutase==
+<StructureSection load='2nnx' size='340' side='right'caption='[[2nnx]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2nnx]] is a 4 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=2NNX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NNX 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]] 2.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</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=2nnx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nnx OCA], [https://pdbe.org/2nnx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nnx RCSB], [https://www.ebi.ac.uk/pdbsum/2nnx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nnx 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.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nn/2nnx_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2nnx ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A subset of superoxide dismutase 1 (Cu/Zn-SOD1) mutants that cause familial amyotrophic lateral sclerosis (FALS) have heightened reactivity with (-)ONOO and H(2)O(2) in vitro. This reactivity requires a copper ion bound in the active site and is a suggested mechanism of motor neuron injury. However, we have found that transgenic mice that express SOD1-H46R/H48Q, which combines natural FALS mutations at ligands for copper and which is inactive, develop motor neuron disease. Using a direct radioactive copper incorporation assay in transfected cells and the established tools of single crystal x-ray diffraction, we now demonstrate that this variant does not stably bind copper. We find that single mutations at copper ligands, including H46R, H48Q, and a quadruple mutant H46R/H48Q/H63G/H120G, also diminish the binding of radioactive copper. Further, using native polyacrylamide gel electrophoresis and a yeast two-hybrid assay, the binding of copper was found to be related to the formation of the stable dimeric enzyme. Collectively, our data demonstrate a relationship between copper and assembly of SOD1 into stable dimers and also define disease-causing SOD1 mutants that are unlikely to robustly produce toxic radicals via copper-mediated chemistry.
-===Crystal Structure of the H46R, H48Q double mutant of human [Cu-Zn] Superoxide Dismutase===
+Disease-associated mutations at copper ligand histidine residues of superoxide dismutase 1 diminish the binding of copper and compromise dimer stability.,Wang J, Caruano-Yzermans A, Rodriguez A, Scheurmann JP, Slunt HH, Cao X, Gitlin J, Hart PJ, Borchelt DR J Biol Chem. 2007 Jan 5;282(1):345-52. Epub 2006 Nov 8. PMID:17092942<ref>PMID:17092942</ref>
-{{ABSTRACT_PUBMED_17092942}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 2nnx" style="background-color:#fffaf0;"></div>
-[[2nnx]] is a 4 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=2NNX OCA].
 ==See Also==
-*[[Superoxide Dismutase|Superoxide Dismutase]]
+*[[Superoxide dismutase 3D structures|Superoxide dismutase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:017092942</ref><ref group="xtra">PMID:019227972</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Superoxide dismutase]]
+[[Category: Large Structures]]
-[[Category: Hart, P J.]]
+[[Category: Hart PJ]]
-[[Category: Schuermann, J P.]]
+[[Category: Schuermann JP]]
-[[Category: Cu-zn superoxide dismutase]]
-[[Category: Familial amyotrophic lateral sclerosis mutant]]
-[[Category: Human]]
-[[Category: Oxidoreductase]]
-[[Category: Superoxide acceptor]]