1iry

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[[Image:1iry.png|left|200px]]
 
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{{STRUCTURE_1iry| PDB=1iry | SCENE= }}
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==Solution structure of the hMTH1, a nucleotide pool sanitization enzyme==
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<StructureSection load='1iry' size='340' side='right'caption='[[1iry]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1iry]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IRY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IRY 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">Solution NMR</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=1iry FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1iry OCA], [https://pdbe.org/1iry PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1iry RCSB], [https://www.ebi.ac.uk/pdbsum/1iry PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1iry ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/8ODP_HUMAN 8ODP_HUMAN] Antimutagenic. Acts as a sanitizing enzyme for oxidized nucleotide pools, thus suppressing cell dysfunction and death induced by oxidative stress. Hydrolyzes 8-oxo-dGTP, 8-oxo-dATP and 2-OH-dATP, thus preventing misincorporation of oxidized purine nucleoside triphosphates into DNA and subsequently preventing A:T to C:G and G:C to T:A transversions. Able to hydrolyze also the corresponding ribonucleotides, 2-OH-ATP, 8-oxo-GTP and 8-oxo-ATP.<ref>PMID:10373420</ref> <ref>PMID:10608900</ref> <ref>PMID:11139615</ref> <ref>PMID:12857738</ref> <ref>PMID:22556419</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/ir/1iry_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=1iry 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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Oxygen radicals generated through normal cellular respiration processes can cause mutations in genomic and mitochondrial DNA. Human MTH1 hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP and 2-hydroxy-dATP, to monophosphates, thereby preventing the misincorporation of these oxidized nucleotides during replication. Here we present the solution structure of MTH1 solved by multidimensional heteronuclear NMR spectroscopy. The protein adopts a fold similar to that of Escherichia coli MutT, despite the low sequence similarity between these proteins outside the conserved Nudix motif. The substrate-binding pocket of MTH1, deduced from chemical shift perturbation experiments, is located at essentially the same position as in MutT; however, a pocket-forming helix is largely displaced in MTH1 (approximately 9 A) such that the shape of the pocket differs between the two proteins. Detailed analysis of the pocket-forming residues enabled us to identify Asn33 as one of the key residues in MTH1 for discriminating the oxidized form of purine, and mutation of this residue modifies the substrate specificity. We also show that MTH1 catalyzes hydrolysis of 8-oxo-dGTP through nucleophilic substitution of water at the beta-phosphate.
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===Solution structure of the hMTH1, a nucleotide pool sanitization enzyme===
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Structure of human MTH1, a Nudix family hydrolase that selectively degrades oxidized purine nucleoside triphosphates.,Mishima M, Sakai Y, Itoh N, Kamiya H, Furuichi M, Takahashi M, Yamagata Y, Iwai S, Nakabeppu Y, Shirakawa M J Biol Chem. 2004 Aug 6;279(32):33806-15. Epub 2004 May 7. PMID:15133035<ref>PMID:15133035</ref>
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{{ABSTRACT_PUBMED_15133035}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1iry" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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[[1iry]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IRY OCA].
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*[[7%2C8-dihydro-8-oxoguanine triphosphatase 3D structures|7%2C8-dihydro-8-oxoguanine triphosphatase 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:015133035</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Itoh, N.]]
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[[Category: Large Structures]]
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[[Category: Kamiya, H.]]
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[[Category: Itoh N]]
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[[Category: Mishima, M.]]
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[[Category: Kamiya H]]
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[[Category: Nakabeppu, Y.]]
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[[Category: Mishima M]]
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[[Category: Sakai, Y.]]
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[[Category: Nakabeppu Y]]
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[[Category: Shirakawa, M.]]
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[[Category: Sakai Y]]
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[[Category: Hydrolase]]
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[[Category: Shirakawa M]]

Current revision

Solution structure of the hMTH1, a nucleotide pool sanitization enzyme

PDB ID 1iry

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