2adp

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[[Image:2adp.gif|left|200px]]<br /><applet load="2adp" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2adp, resolution 2.4&Aring;" />
 
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'''Nitrated Human Manganese Superoxide Dismutase'''<br />
 
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==Overview==
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==Nitrated Human Manganese Superoxide Dismutase==
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A cellular consequence of the reaction of superoxide and nitric oxide is enhanced peroxynitrite levels. Reaction of peroxynitrite with manganese superoxide dismutase (MnSOD) causes nitration of the active-site residue Tyr34 and nearly complete inhibition of catalysis. We report the crystal structures at 2.4 A resolution of human MnSOD nitrated by peroxynitrite and the unmodified MnSOD. A comparison of these structures showed no significant conformational changes of active-site residues or solvent displacement. The side chain of 3-nitrotyrosine 34 had a single conformation that extended toward the manganese with O1 of the nitro group within hydrogen-bonding distance (3.1 A) of Nepsilon2 of the second-shell ligand Gln143. Also, nitration of Tyr34 caused a weakening, as evidenced by the lengthening, of a hydrogen bond between its phenolic OH and Gln143, part of an extensive hydrogen-bond network in the active site. Inhibition of catalysis can be attributed to a steric effect of 3-nitrotyrosine 34 that impedes substrate access and binding, and alteration of the hydrogen-bond network that supports proton transfer in catalysis. It is also possible that an electrostatic effect of the nitro group has altered the finely tuned redox potential necessary for efficient catalysis, although the redox potential of nitrated MnSOD has not been measured.
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<StructureSection load='2adp' size='340' side='right'caption='[[2adp]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2adp]] is a 1 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=2ADP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ADP FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NIY:META-NITRO-TYROSINE'>NIY</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2adp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2adp OCA], [https://pdbe.org/2adp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2adp RCSB], [https://www.ebi.ac.uk/pdbsum/2adp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2adp ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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.
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ad/2adp_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2adp ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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2ADP 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 <scene name='pdbligand=MN:'>MN</scene> and <scene name='pdbligand=K:'>K</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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://oca.weizmann.ac.il/oca-bin/ocashort?id=2ADP OCA].
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*[[Superoxide dismutase 3D structures|Superoxide dismutase 3D structures]]
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== References ==
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==Reference==
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<references/>
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Crystal structure of nitrated human manganese superoxide dismutase: mechanism of inactivation., Quint P, Reutzel R, Mikulski R, McKenna R, Silverman DN, Free Radic Biol Med. 2006 Feb 1;40(3):453-8. Epub 2005 Nov 9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16443160 16443160]
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Superoxide dismutase]]
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[[Category: McKenna R]]
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[[Category: McKenna, R.]]
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[[Category: Mikulski R]]
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[[Category: Mikulski, R.]]
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[[Category: Quint P]]
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[[Category: Quint, P.]]
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[[Category: Reutzel R]]
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[[Category: Reutzel, R.]]
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[[Category: Silverman DN]]
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[[Category: Silverman, D N.]]
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[[Category: K]]
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[[Category: MN]]
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[[Category: oxidoreductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:26:21 2008''
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Current revision

Nitrated Human Manganese Superoxide Dismutase

PDB ID 2adp

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