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| | ==Crystal Structure of the Y34F mutant of Saccharomyces cerevisiae Manganese Superoxide Dismutase== | | ==Crystal Structure of the Y34F mutant of Saccharomyces cerevisiae Manganese Superoxide Dismutase== |
| - | <StructureSection load='4e4e' size='340' side='right' caption='[[4e4e]], [[Resolution|resolution]] 1.88Å' scene=''> | + | <StructureSection load='4e4e' size='340' side='right'caption='[[4e4e]], [[Resolution|resolution]] 1.88Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4e4e]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E4E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E4E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4e4e]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E4E FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.88Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SOD2, YHR008C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae])</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=4e4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4e OCA], [https://pdbe.org/4e4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e4e RCSB], [https://www.ebi.ac.uk/pdbsum/4e4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e4e ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4e4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e4e RCSB], [http://www.ebi.ac.uk/pdbsum/4e4e PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SODM_YEAST SODM_YEAST]] Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems. | + | [https://www.uniprot.org/uniprot/SODM_YEAST SODM_YEAST] Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems. |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Reduction of superoxide ( ) by manganese-containing superoxide dismutase occurs through either a "prompt protonation" pathway, or an "inner-sphere" pathway, with the latter leading to formation of an observable Mn-peroxo complex. We recently reported that wild-type (WT) manganese superoxide dismutases (MnSODs) from Saccharomyces cerevisiae and Candida albicans are more gated toward the "prompt protonation" pathway than human and bacterial MnSODs and suggested that this could result from small structural changes in the second coordination sphere of manganese. We report here that substitution of a second-sphere residue, Tyr34, by phenylalanine (Y34F) causes the MnSOD from S. cerevisiae to react exclusively through the "inner-sphere" pathway. At neutral pH, we have a surprising observation that protonation of the Mn-peroxo complex in the mutant yeast enzyme occurs through a fast pathway, leading to a putative six-coordinate Mn(3+) species, which actively oxidizes in the catalytic cycle. Upon increasing pH, the fast pathway is gradually replaced by a slow proton-transfer pathway, leading to the well-characterized five-coordinate Mn(3+). We here propose and compare two hypothetical mechanisms for the mutant yeast enzyme, differing in the structure of the Mn-peroxo complex yet both involving formation of the active six-coordinate Mn(3+) and proton transfer from a second-sphere water molecule, which has substituted for the horizontal line OH of Tyr34, to the Mn-peroxo complex. Because WT and the mutant yeast MnSOD both rest in the 2+ state and become six-coordinate when oxidized up from Mn(2+), six-coordinate Mn(3+) species could also actively function in the mechanism of WT yeast MnSODs.
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| - | Six-coordinate manganese(3+) in catalysis by yeast manganese superoxide dismutase.,Sheng Y, Butler Gralla E, Schumacher M, Cascio D, Cabelli DE, Selverstone Valentine J Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14314-9. Epub 2012 Aug 20. PMID:22908245<ref>PMID:22908245</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| | ==See Also== | | ==See Also== |
| - | *[[Superoxide Dismutase|Superoxide Dismutase]] | + | *[[Superoxide dismutase 3D structures|Superoxide dismutase 3D structures]] |
| - | == References ==
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| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Saccharomyces cerevisiae]] | | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Superoxide dismutase]]
| + | [[Category: Cascio D]] |
| - | [[Category: Cascio, D]] | + | [[Category: Sheng Y]] |
| - | [[Category: Sheng, Y]] | + | [[Category: Valentine JS]] |
| - | [[Category: Valentine, J S]] | + | |
| - | [[Category: Mn superoxide dismutase]]
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| - | [[Category: Oxidoreductase]]
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