1uxm: Difference between revisions

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-[[Image:1uxm.png|left|200px]]
-<!--
+==A4V mutant of human SOD1==
-The line below this paragraph, containing "STRUCTURE_1uxm", creates the "Structure Box" on the page.
+<StructureSection load='1uxm' size='340' side='right'caption='[[1uxm]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1uxm]] is a 12 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=1UXM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UXM FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_1uxm|  PDB=1uxm  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1uxm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uxm OCA], [https://pdbe.org/1uxm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uxm RCSB], [https://www.ebi.ac.uk/pdbsum/1uxm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uxm 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/ux/1uxm_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1uxm ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+More than 90 point mutations in human CuZn superoxide dismutase lead to the development of familial amyotrophic lateral sclerosis, known also as motor neuron disease. A growing body of evidence suggests that a subset of mutations located close to the dimeric interface can lead to a major destabilization of the mutant enzymes. We have determined the crystal structures of the Ala4Val (A4V) and Ile113Thr (I113T) mutants to 1.9 and 1.6 A, respectively. In the A4V structure, small changes at the dimer interface result in a substantial reorientation of the two monomers. This effect is also seen in the case of the I113T crystal structure, but to a smaller extent. X-ray solution scattering data show that in the solution state, both of the mutants undergo a more pronounced conformational change compared with wild-type superoxide dismutase (SOD) than that observed in the A4V crystal structure. Shape reconstructions from the x-ray scattering data illustrate the nature of this destabilization. Comparison of these scattering data with those for bovine CuZn SOD measured at different temperatures shows that an analogous change in the scattering profile occurs for the bovine enzyme in the temperature range of 70-80 degrees C. These results demonstrate that the A4V and I113T mutants are substantially destabilized in comparison with wild-type SOD1, and it is possible that the pathogenic properties of this subset of familial amyotrophic lateral sclerosis mutants are at least in part due to this destabilization.
-===A4V MUTANT OF HUMAN SOD1===
+Dimer destabilization in superoxide dismutase may result in disease-causing properties: structures of motor neuron disease mutants.,Hough MA, Grossmann JG, Antonyuk SV, Strange RW, Doucette PA, Rodriguez JA, Whitson LJ, Hart PJ, Hayward LJ, Valentine JS, Hasnain SS Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5976-81. Epub 2004 Mar 31. PMID:15056757<ref>PMID:15056757</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<!--
+</div>
-The line below this paragraph, {{ABSTRACT_PUBMED_15056757}}, adds the Publication Abstract to the page
+<div class="pdbe-citations 1uxm" style="background-color:#fffaf0;"></div>
-(as it appears on PubMed at http://www.pubmed.gov), where 15056757 is the PubMed ID number.
--->
-{{ABSTRACT_PUBMED_15056757}}
-==About this Structure==
-[[1uxm]] is a 12 chain structure of [[Superoxide Dismutase]] 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=1UXM OCA].
 ==See Also==
-*[[Superoxide Dismutase]]
+*[[Superoxide dismutase 3D structures|Superoxide dismutase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:015056757</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Superoxide dismutase]]
+[[Category: Large Structures]]
-[[Category: Antonyuk, S V.]]
+[[Category: Antonyuk SV]]
-[[Category: Doucette, P A.]]
+[[Category: Doucette PA]]
-[[Category: Grossmann, J G.]]
+[[Category: Grossmann JG]]
-[[Category: Hart, P J.]]
+[[Category: Hart PJ]]
-[[Category: Hasnain, S S.]]
+[[Category: Hasnain SS]]
-[[Category: Hayward, L J.]]
+[[Category: Hayward LJ]]
-[[Category: Hough, M A.]]
+[[Category: Hough MA]]
-[[Category: Rodriguez, J A.]]
+[[Category: Rodriguez JA]]
-[[Category: Strange, R W.]]
+[[Category: Strange RW]]
-[[Category: Valentine, J S.]]
+[[Category: Valentine JS]]
-[[Category: Whitson, L J.]]
+[[Category: Whitson LJ]]
-[[Category: Amyotrophic lateral sclerosis]]
-[[Category: Antioxidant]]
-[[Category: Disease mutation]]
-[[Category: Human cu]]
-[[Category: Metal- binding]]
-[[Category: Oxidoreductase]]
-[[Category: Zn superoxide dismutase]]