1pu0

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[[Image:1pu0.gif|left|200px]]
 
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{{Structure
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==Structure of Human Cu,Zn Superoxide Dismutase==
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|PDB= 1pu0 |SIZE=350|CAPTION= <scene name='initialview01'>1pu0</scene>, resolution 1.70&Aring;
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<StructureSection load='1pu0' size='340' side='right'caption='[[1pu0]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=CU1:COPPER+(I)+ION'>CU1</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene>
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<table><tr><td colspan='2'>[[1pu0]] is a 10 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=1PU0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PU0 FirstGlance]. <br>
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|ACTIVITY= [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]
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
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|GENE= SOD1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CU1:COPPER+(I)+ION'>CU1</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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}}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1pu0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pu0 OCA], [https://pdbe.org/1pu0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pu0 RCSB], [https://www.ebi.ac.uk/pdbsum/1pu0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pu0 ProSAT]</span></td></tr>
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</table>
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'''Structure of Human Cu,Zn Superoxide Dismutase'''
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== Disease ==
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[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>
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== Function ==
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==Overview==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pu/1pu0_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1pu0 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
Many point mutations in human Cu,Zn superoxide dismutase (SOD) cause familial amyotrophic lateral sclerosis (FALS), a fatal neurodegenerative disorder in heterozygotes. Here we show that these mutations cluster in protein regions influencing architectural integrity. Furthermore, crystal structures of SOD wild-type and FALS mutant H43R proteins uncover resulting local framework defects. Characterizations of beta-barrel (H43R) and dimer interface (A4V) FALS mutants reveal reduced stability and drastically increased aggregation propensity. Moreover, electron and atomic force microscopy indicate that these defects promote the formation of filamentous aggregates. The filaments resemble those seen in neurons of FALS patients and bind both Congo red and thioflavin T, suggesting the presence of amyloid-like, stacked beta-sheet interactions. These results support free-cysteine-independent aggregation of FALS mutant SOD as an integral part of FALS pathology. They furthermore provide a molecular basis for the single FALS disease phenotype resulting from mutations of diverse side-chains throughout the protein: many FALS mutations reduce structural integrity, lowering the energy barrier for fibrous aggregation.
Many point mutations in human Cu,Zn superoxide dismutase (SOD) cause familial amyotrophic lateral sclerosis (FALS), a fatal neurodegenerative disorder in heterozygotes. Here we show that these mutations cluster in protein regions influencing architectural integrity. Furthermore, crystal structures of SOD wild-type and FALS mutant H43R proteins uncover resulting local framework defects. Characterizations of beta-barrel (H43R) and dimer interface (A4V) FALS mutants reveal reduced stability and drastically increased aggregation propensity. Moreover, electron and atomic force microscopy indicate that these defects promote the formation of filamentous aggregates. The filaments resemble those seen in neurons of FALS patients and bind both Congo red and thioflavin T, suggesting the presence of amyloid-like, stacked beta-sheet interactions. These results support free-cysteine-independent aggregation of FALS mutant SOD as an integral part of FALS pathology. They furthermore provide a molecular basis for the single FALS disease phenotype resulting from mutations of diverse side-chains throughout the protein: many FALS mutations reduce structural integrity, lowering the energy barrier for fibrous aggregation.
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==Disease==
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ALS mutants of human superoxide dismutase form fibrous aggregates via framework destabilization.,DiDonato M, Craig L, Huff ME, Thayer MM, Cardoso RM, Kassmann CJ, Lo TP, Bruns CK, Powers ET, Kelly JW, Getzoff ED, Tainer JA J Mol Biol. 2003 Sep 19;332(3):601-15. PMID:12963370<ref>PMID:12963370</ref>
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Known disease associated with this structure: Amyotrophic lateral sclerosis, due to SOD1 deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147450 147450]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1PU0 is a [[Single protein]] structure of 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=1PU0 OCA].
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</div>
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<div class="pdbe-citations 1pu0" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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ALS mutants of human superoxide dismutase form fibrous aggregates via framework destabilization., DiDonato M, Craig L, Huff ME, Thayer MM, Cardoso RM, Kassmann CJ, Lo TP, Bruns CK, Powers ET, Kelly JW, Getzoff ED, Tainer JA, J Mol Biol. 2003 Sep 19;332(3):601-15. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12963370 12963370]
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*[[Superoxide dismutase 3D structures|Superoxide dismutase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Superoxide dismutase]]
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[[Category: Bruns CK]]
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[[Category: Bruns, C K.]]
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[[Category: Cardoso RMF]]
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[[Category: Cardoso, R M.F.]]
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[[Category: Craig L]]
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[[Category: Craig, L.]]
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[[Category: DiDonato M]]
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[[Category: DiDonato, M.]]
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[[Category: Getzoff ED]]
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[[Category: Getzoff, E D.]]
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[[Category: Huff ME]]
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[[Category: Huff, M E.]]
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[[Category: Kassmann CJ]]
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[[Category: Kassmann, C J.]]
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[[Category: Kelly JW]]
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[[Category: Kelly, J W.]]
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[[Category: Lo TP]]
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[[Category: Lo, T P.]]
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[[Category: Powers ET]]
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[[Category: Powers, E T.]]
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[[Category: Tainer JA]]
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[[Category: Tainer, J A.]]
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[[Category: Thayer MM]]
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[[Category: Thayer, M M.]]
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[[Category: CU1]]
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[[Category: SO4]]
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[[Category: ZN]]
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[[Category: al]]
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[[Category: fal]]
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[[Category: lou gehrig's disease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:28:56 2008''
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Current revision

Structure of Human Cu,Zn Superoxide Dismutase

PDB ID 1pu0

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