1pm9

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(New page: 200px<br /> <applet load="1pm9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pm9, resolution 1.70&Aring;" /> '''CRYSTAL STRUCTURE O...)
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[[Image:1pm9.gif|left|200px]]<br />
 
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<applet load="1pm9" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1pm9, resolution 1.70&Aring;" />
 
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'''CRYSTAL STRUCTURE OF HUMAN MNSOD H30N, Y166F MUTANT'''<br />
 
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==Overview==
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==CRYSTAL STRUCTURE OF HUMAN MNSOD H30N, Y166F MUTANT==
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The side chains of His30 and Tyr166 from adjacent subunits in the, homotetramer human manganese superoxide dismutase (Mn-SOD) form a hydrogen, bond across the dimer interface and participate in a hydrogen-bonded, network that extends to the active site. Compared with wild-type Mn-SOD, the site-specific mutants H30N, Y166F, and the corresponding double mutant, showed 10-fold decreases in steady-state constants for catalysis measured, by pulse radiolysis. The observation of no additional effect upon the, second mutation is an example of cooperatively interacting residues. A, similar effect was observed in the thermal stability of these enzymes; the, double mutant did not reduce the major unfolding transition to an extent, greater than either single mutant. The crystal structures of these, site-specific mutants each have unique conformational changes, but each, has lost the hydrogen bond across the dimer interface, which results in a, decrease in catalysis. These same mutations caused an enhancement of the, dissociation of the product-inhibited complex. That is, His30 and Tyr166, in wild-type Mn-SOD act to prolong the lifetime of the inhibited complex., This would have a selective advantage in blocking a cellular, overproduction of toxic H2O2.
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<StructureSection load='1pm9' size='340' side='right'caption='[[1pm9]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1pm9]] 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=1PM9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PM9 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]] 1.7&#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=MN3:MANGANESE+(III)+ION'>MN3</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=1pm9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pm9 OCA], [https://pdbe.org/1pm9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pm9 RCSB], [https://www.ebi.ac.uk/pdbsum/1pm9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pm9 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/pm/1pm9_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=1pm9 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The side chains of His30 and Tyr166 from adjacent subunits in the homotetramer human manganese superoxide dismutase (Mn-SOD) form a hydrogen bond across the dimer interface and participate in a hydrogen-bonded network that extends to the active site. Compared with wild-type Mn-SOD, the site-specific mutants H30N, Y166F, and the corresponding double mutant showed 10-fold decreases in steady-state constants for catalysis measured by pulse radiolysis. The observation of no additional effect upon the second mutation is an example of cooperatively interacting residues. A similar effect was observed in the thermal stability of these enzymes; the double mutant did not reduce the major unfolding transition to an extent greater than either single mutant. The crystal structures of these site-specific mutants each have unique conformational changes, but each has lost the hydrogen bond across the dimer interface, which results in a decrease in catalysis. These same mutations caused an enhancement of the dissociation of the product-inhibited complex. That is, His30 and Tyr166 in wild-type Mn-SOD act to prolong the lifetime of the inhibited complex. This would have a selective advantage in blocking a cellular overproduction of toxic H2O2.
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==About this Structure==
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Amino acid substitution at the dimeric interface of human manganese superoxide dismutase.,Hearn AS, Fan L, Lepock JR, Luba JP, Greenleaf WB, Cabelli DE, Tainer JA, Nick HS, Silverman DN J Biol Chem. 2004 Feb 13;279(7):5861-6. Epub 2003 Nov 24. PMID:14638684<ref>PMID:14638684</ref>
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1PM9 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=1PM9 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Amino acid substitution at the dimeric interface of human manganese superoxide dismutase., Hearn AS, Fan L, Lepock JR, Luba JP, Greenleaf WB, Cabelli DE, Tainer JA, Nick HS, Silverman DN, J Biol Chem. 2004 Feb 13;279(7):5861-6. Epub 2003 Nov 24. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14638684 14638684]
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</div>
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[[Category: Homo sapiens]]
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<div class="pdbe-citations 1pm9" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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[[Category: Superoxide dismutase]]
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[[Category: Fan, L.]]
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[[Category: Tainer, J.A.]]
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[[Category: MN3]]
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[[Category: oxidoreductase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:45:14 2007''
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==See Also==
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*[[Superoxide dismutase 3D structures|Superoxide dismutase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Fan L]]
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[[Category: Tainer JA]]

Current revision

CRYSTAL STRUCTURE OF HUMAN MNSOD H30N, Y166F MUTANT

PDB ID 1pm9

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