1var: Difference between revisions

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New page: left|200px<br /> <applet load="1var" size="450" color="white" frame="true" align="right" spinBox="true" caption="1var, resolution 2.5Å" /> '''MITOCHONDRIAL MANGAN...
 
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[[Image:1var.gif|left|200px]]<br />
<applet load="1var" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1var, resolution 2.5&Aring;" />
'''MITOCHONDRIAL MANGANESE SUPEROXIDE DISMUTASE VARIANT WITH ILE 58 REPLACED BY THR'''<br />


==Overview==
==MITOCHONDRIAL MANGANESE SUPEROXIDE DISMUTASE VARIANT WITH ILE 58 REPLACED BY THR==
Human manganese superoxide dismutase (MnSOD) is a homotetrameric enzyme, which protects mitochondria against oxygen-mediated free radical damage., Within each subunit, both the N-terminal helical hairpin and C-terminal, alpha/beta domains contribute ligands to the catalytic manganese site. Two, identical four-helix bundles, symmetrically assembled from the N-terminal, helical hairpins, form a novel tetrameric interface that stabilizes the, active sites. The 2.5 A crystallographic structure of the naturally, occurring polymorphic variant Ile58Thr MnSOD reveals that the helical, hairpin mutation Thr58 causes two packing defects in each of the two, four-helix bundles of the tetrameric interface. Similar mutations, expected to cause packing defects in the Cu,ZnSOD dimer interface, are, associated with the degenerative disease amyotrophic lateral sclerosis., Ile58Thr MnSOD is primarily dimeric in solution and is significantly less, thermostable than the normal enzyme, with decreases of 15 degrees C in the, main melting temperature and 20 degrees C in the heat-inactivation, temperature. Consequently, this mutant MnSOD is compromised at normal body, temperatures: thermal inactivation, predicted from the decrease in thermal, stability, occurs with a theoretical half-life of only 3.2 h at 37 degrees, C (1.4 h at 41 degrees C), compared with 3.1 years for native MnSOD. This, prediction is supported by direct measurements: incubation at 41.7 degrees, C for 3 h has no effect on the activity of native MnSOD but completely, inactivates mutant MnSOD. Rapid inactivation of Ile58Thr MnSOD at the, elevated temperatures associated with fever and inflammation could provide, an early advantage by killing infected cells, but also would increase, superoxide-mediated oxidative damage and perhaps contribute to late-onset, diseases.
<StructureSection load='1var' size='340' side='right'caption='[[1var]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1var]] is a 2 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=1VAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1VAR 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]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN3:MANGANESE+(III)+ION'>MN3</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=1var FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1var OCA], [https://pdbe.org/1var PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1var RCSB], [https://www.ebi.ac.uk/pdbsum/1var PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1var 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/va/1var_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=1var ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1VAR 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 MN3 as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1VAR OCA].
*[[Superoxide dismutase 3D structures|Superoxide dismutase 3D structures]]
 
== References ==
==Reference==
<references/>
Human mitochondrial manganese superoxide dismutase polymorphic variant Ile58Thr reduces activity by destabilizing the tetrameric interface., Borgstahl GE, Parge HE, Hickey MJ, Johnson MJ, Boissinot M, Hallewell RA, Lepock JR, Cabelli DE, Tainer JA, Biochemistry. 1996 Apr 9;35(14):4287-97. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8605177 8605177]
__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: MN3]]
[[Category: manganese]]
[[Category: mitochondrion]]
[[Category: oxidoreductase]]
[[Category: polymorphism]]
[[Category: transit peptide]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:42:41 2007''

Latest revision as of 11:45, 14 February 2024

MITOCHONDRIAL MANGANESE SUPEROXIDE DISMUTASE VARIANT WITH ILE 58 REPLACED BY THRMITOCHONDRIAL MANGANESE SUPEROXIDE DISMUTASE VARIANT WITH ILE 58 REPLACED BY THR

Structural highlights

1var is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.5Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SODM_HUMAN Genetic variation in SOD2 is associated with susceptibility to microvascular complications of diabetes type 6 (MVCD6) [MIM: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

SODM_HUMAN Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ MacMillan-Crow LA, Thompson JA. Tyrosine modifications and inactivation of active site manganese superoxide dismutase mutant (Y34F) by peroxynitrite. Arch Biochem Biophys. 1999 Jun 1;366(1):82-8. PMID:10334867 doi:S0003-9861(99)91202-X

1var, resolution 2.50Å

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