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| | ==Contribution to Structure and Catalysis of Tyrosine 34 in Human Manganese Superoxide Dismutase== | | ==Contribution to Structure and Catalysis of Tyrosine 34 in Human Manganese Superoxide Dismutase== |
| - | <StructureSection load='1zuq' size='340' side='right' caption='[[1zuq]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='1zuq' size='340' side='right'caption='[[1zuq]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1zuq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZUQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ZUQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1zuq]] 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=1ZUQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZUQ 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]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1zsp|1zsp]], [[1zte|1zte]]</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SOD2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1zuq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zuq OCA], [https://pdbe.org/1zuq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zuq RCSB], [https://www.ebi.ac.uk/pdbsum/1zuq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zuq 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>
| + | |
| - | <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=1zuq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zuq OCA], [http://pdbe.org/1zuq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zuq RCSB], [http://www.ebi.ac.uk/pdbsum/1zuq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1zuq ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://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:[http://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. | + | [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 == | | == Function == |
| - | [[http://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> | + | [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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 1zuq" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 1zuq" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Superoxide dismutase 3D structures|Superoxide dismutase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Superoxide dismutase]] | + | [[Category: Large Structures]] |
| - | [[Category: Cabelii, D E]] | + | [[Category: Cabelii DE]] |
| - | [[Category: Hearn, A S]] | + | [[Category: Hearn AS]] |
| - | [[Category: Nick, H S]] | + | [[Category: Nick HS]] |
| - | [[Category: Perry, J J]] | + | [[Category: Perry JJ]] |
| - | [[Category: Silverman, D S]] | + | [[Category: Silverman DS]] |
| - | [[Category: Tainer, J A]] | + | [[Category: Tainer JA]] |
| - | [[Category: Manganese superoxide dismutase]]
| + | |
| - | [[Category: Mnsod]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Y34v mutation]]
| + | |
| Structural highlights
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.
Publication Abstract from PubMed
Superoxide dismutase (SOD) enzymes are critical in controlling levels of reactive oxygen species (ROS) that are linked to aging, cancer, and neurodegenerative disease. Superoxide (O(2)(*-)) produced during respiration is removed by the product of the SOD2 gene, the homotetrameric manganese superoxide dismutase (MnSOD). Here, we examine the structural and catalytic roles of the highly conserved active-site residue Tyr34, based upon structure-function studies of MnSOD enzymes with mutations at this site. Substitution of Tyr34 with five different amino acids retained the active-site protein structure and assembly but caused a substantial decrease in the catalytic rate constant for the reduction of superoxide. The rate constant for formation of the product inhibition complex also decreases but to a much lesser extent, resulting in a net increase in the level of product inhibited form of the mutant enzymes. Comparisons of crystal structures and catalytic rates also suggest that one mutation, Y34V, interrupts the hydrogen-bonded network, which is associated with a rapid dissociation of the product-inhibited complex. Notably, with three of the Tyr34 mutants, we also observe an intermediate in catalysis, which has not been reported previously. Thus, these mutants establish a means of trapping a catalytic intermediate that promises to help elucidate the mechanism of catalysis.
Contribution of Human Manganese Superoxide Dismutase Tyrosine 34 to Structure and Catalysis (dagger).,Perry JJ, Hearn AS, Cabelli DE, Nick HS, Tainer JA, Silverman DN Biochemistry. 2009 Mar 27. PMID:19265433[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ Perry JJ, Hearn AS, Cabelli DE, Nick HS, Tainer JA, Silverman DN. Contribution of Human Manganese Superoxide Dismutase Tyrosine 34 to Structure and Catalysis (dagger). Biochemistry. 2009 Mar 27. PMID:19265433 doi:10.1021/bi8023288
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