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New page: left|200px<br /> <applet load="1n0j" size="450" color="white" frame="true" align="right" spinBox="true" caption="1n0j, resolution 2.2Å" /> '''The Structure of Hum...
 
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[[Image:1n0j.gif|left|200px]]<br />
<applet load="1n0j" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1n0j, resolution 2.2&Aring;" />
'''The Structure of Human Mitochondrial MN3+ Superoxide Dismutase Reveals a Novel Tetrameric Interface of Two 4-Helix Bundles'''<br />


==Overview==
==The Structure of Human Mitochondrial MN3+ Superoxide Dismutase Reveals a Novel Tetrameric Interface of Two 4-Helix Bundles==
The 2.2 A resolution crystal structure of recombinant human manganese, superoxide dismutase, a homotetrameric enzyme that protects mitochondria, against oxygen-mediated free radical damage, has been determined. Within, each subunit, both the N-terminal helical hairpin and C-terminal, alpha/beta domains contribute ligands to the catalytic manganese site. Two, identical 4-helix bundles, symmetrically assembled from the N-terminal, helical hairpins, form novel tetrameric interfaces that stabilize the, active sites. Structurally altered polymorphic variants with reduced, activity, such as tetrameric interface mutant Ile-58 to Thr, may produce, not only an early selective advantage, through enhanced cytotoxicity of, tumor necrosis factor for virus-infected cells, but also detrimental, effects from increased mitochondrial oxidative damage, contributing to, degenerative conditions, including diabetes, aging, and Parkinson's and, Alzheimer's diseases.
<StructureSection load='1n0j' size='340' side='right'caption='[[1n0j]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1n0j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1abm 1abm]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N0J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N0J 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=1n0j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n0j OCA], [https://pdbe.org/1n0j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n0j RCSB], [https://www.ebi.ac.uk/pdbsum/1n0j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n0j ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SODM_HUMAN SODM_HUMAN] Genetic variation in SOD2 is associated with susceptibility to microvascular complications of diabetes type 6 (MVCD6) [MIM:[https://omim.org/entry/612634 612634]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.
== Function ==
[https://www.uniprot.org/uniprot/SODM_HUMAN SODM_HUMAN] Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.<ref>PMID:10334867</ref>
== 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/n0/1n0j_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=1n0j ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1N0J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MN as [http://en.wikipedia.org/wiki/ligand ligand]. This structure superseeds the now removed PDB entry 1ABM. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1N0J OCA].
*[[Superoxide dismutase 3D structures|Superoxide dismutase 3D structures]]
 
== References ==
==Reference==
<references/>
The structure of human mitochondrial manganese superoxide dismutase reveals a novel tetrameric interface of two 4-helix bundles., Borgstahl GE, Parge HE, Hickey MJ, Beyer WF Jr, Hallewell RA, Tainer JA, Cell. 1992 Oct 2;71(1):107-18. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=1394426 1394426]
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Superoxide dismutase]]
[[Category: Borgstahl GEO]]
[[Category: Borgstahl, G.E.O.]]
[[Category: Parge HE]]
[[Category: Parge, H.E.]]
[[Category: Tainer JA]]
[[Category: Tainer, J.A.]]
[[Category: MN]]
[[Category: four-helix bundle]]
[[Category: manganese]]
[[Category: metalloenzyme]]
 
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