1ja8: Difference between revisions
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<StructureSection load='1ja8' size='340' side='right'caption='[[1ja8]], [[Resolution|resolution]] 2.12Å' scene=''> | <StructureSection load='1ja8' size='340' side='right'caption='[[1ja8]], [[Resolution|resolution]] 2.12Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1ja8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[1ja8]] 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=1JA8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JA8 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.12Å</td></tr> | ||
<tr id=' | <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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1ja8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ja8 OCA], [https://pdbe.org/1ja8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ja8 RCSB], [https://www.ebi.ac.uk/pdbsum/1ja8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ja8 ProSAT]</span></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=1ja8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ja8 OCA], [https://pdbe.org/1ja8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ja8 RCSB], [https://www.ebi.ac.uk/pdbsum/1ja8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ja8 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == 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 == | == 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 == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Cabelli DE]] | |||
[[Category: Cabelli | [[Category: Hearn AS]] | ||
[[Category: Hearn | [[Category: Lepock JR]] | ||
[[Category: Lepock | [[Category: Nick HS]] | ||
[[Category: Nick | [[Category: Silverman DS]] | ||
[[Category: Silverman | [[Category: Stroupe ME]] | ||
[[Category: Stroupe | [[Category: Tainer JA]] | ||
[[Category: Tainer | |||
Latest revision as of 11:37, 16 August 2023
Kinetic Analysis of Product Inhibition in Human Manganese Superoxide DismutaseKinetic Analysis of Product Inhibition in Human Manganese Superoxide Dismutase
Structural highlights
DiseaseSODM_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. FunctionSODM_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 PubMedManganese superoxide dismutase (MnSOD) cycles between the Mn(II) and Mn(III) states during the catalyzed disproportionation of O(2)(*-), a catalysis that is limited at micromolar levels of superoxide by a peroxide-inhibited complex with the metal. We have investigated the role in catalysis and inhibition of the conserved residue Trp161 which forms a hydrophobic side of the active site cavity of MnSOD. Crystal structures of mutants of human MnSOD in which Trp161 was replaced with Ala or Phe showed significant conformational changes on adjacent residues near the active site, particularly Gln143 and Tyr34 which in wild-type MnSOD participate in a hydrogen bond network believed to support proton transfer during catalysis. Using pulse radiolysis and observing the UV absorbance of superoxide, we have determined rate constants for the catalytic dismutation of superoxide. In addition, the rates of formation and dissociation of the product-inhibited complex of these mutants were determined by direct observation of the characteristic visible absorption of the oxidized and inhibited states. Catalysis by W161A and W161F MnSOD was associated with a decrease of at least 100-fold in the catalytic rate of reduction of superoxide, which then promotes a competing pathway leading to product inhibition. The structural changes caused by the mutations at position 161 led to small changes, at most a 6-fold decrease, in the rate constant for formation of the inhibited complex. Solvent hydrogen isotope effects support a mechanism in which formation of this complex, presumably the peroxide dianion bound to the manganese, involves no rate-contributing proton transfer; however, the dissociation of the complex requires proton transfer to generate HO(2)(-) or H2O2. Kinetic analysis of product inhibition in human manganese superoxide dismutase.,Hearn AS, Stroupe ME, Cabelli DE, Lepock JR, Tainer JA, Nick HS, Silverman DN Biochemistry. 2001 Oct 9;40(40):12051-8. PMID:11580280[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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