5gho

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==Crystal structure of human MTH1(G2K/D120A mutant) in complex with 8-oxo-dGTP==
==Crystal structure of human MTH1(G2K/D120A mutant) in complex with 8-oxo-dGTP==
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<StructureSection load='5gho' size='340' side='right' caption='[[5gho]], [[Resolution|resolution]] 1.19&Aring;' scene=''>
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<StructureSection load='5gho' size='340' side='right'caption='[[5gho]], [[Resolution|resolution]] 1.19&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5gho]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GHO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GHO FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5gho]] 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=5GHO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GHO FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8DG:8-OXO-2-DEOXYGUANOSINE-5-TRIPHOSPHATE'>8DG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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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]] 1.191&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ghi|5ghi]], [[5ghj|5ghj]], [[5ghm|5ghm]], [[5ghn|5ghn]], [[5ghp|5ghp]], [[5ghq|5ghq]]</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=8DG:8-OXO-2-DEOXYGUANOSINE-5-TRIPHOSPHATE'>8DG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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<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=5gho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gho OCA], [http://pdbe.org/5gho PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gho RCSB], [http://www.ebi.ac.uk/pdbsum/5gho PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gho ProSAT]</span></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=5gho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gho OCA], [https://pdbe.org/5gho PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gho RCSB], [https://www.ebi.ac.uk/pdbsum/5gho PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gho ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://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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[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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Human MTH1 (hMTH1) is an enzyme that hydrolyses several oxidized purine nucleoside triphosphates to their corresponding nucleoside monophosphates. Crystallographic studies have shown that the accurate mode of interaction between 8-oxoguanine and hMTH1 cannot be understood without determining the positions of the H atoms, as can be observed in neutron and/or ultrahigh-resolution X-ray diffraction studies. The hMTH1 protein prepared in the original expression system from Escherichia coli did not appear to be suitable for obtaining high-quality crystals because the hMTH1 protein had heterogeneous N-termini of Met1 and Gly2 that resulted from N-terminal Met excision by methionine aminopeptidase from the E. coli host. To obtain homogeneous hMTH1, the Gly at the second position was replaced by Lys. As a result, mutant hMTH1 protein [hMTH1(G2K)] with a homogeneous N-terminus could be prepared and high-quality crystals which diffracted to near 1.1 A resolution using synchrotron radiation were produced. The new crystals belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 46.36, b = 47.58, c = 123.89 A.
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Crystallization and preliminary X-ray analysis of human MTH1 with a homogeneous N-terminus.,Koga Y, Inazato M, Nakamura T, Hashikawa C, Chirifu M, Michi A, Yamashita T, Toma S, Kuniyasu A, Ikemizu S, Nakabeppu Y, Yamagata Y Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Jan 1;69(Pt 1):45-8. doi: , 10.1107/S1744309112048002. Epub 2012 Dec 20. PMID:23295485<ref>PMID:23295485</ref>
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==See Also==
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*[[7%2C8-dihydro-8-oxoguanine triphosphatase 3D structures|7%2C8-dihydro-8-oxoguanine triphosphatase 3D structures]]
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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 5gho" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Hirata, K]]
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[[Category: Homo sapiens]]
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[[Category: Nakabeppu, Y]]
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[[Category: Large Structures]]
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[[Category: Nakamura, T]]
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[[Category: Hirata K]]
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[[Category: Waz, S]]
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[[Category: Nakabeppu Y]]
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[[Category: Yamagata, Y]]
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[[Category: Nakamura T]]
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[[Category: Alpha-beta-alpha sandwich]]
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[[Category: Waz S]]
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[[Category: Dna damage]]
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[[Category: Yamagata Y]]
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[[Category: Dna repair]]
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[[Category: Dna replication]]
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[[Category: Hydrolase]]
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Current revision

Crystal structure of human MTH1(G2K/D120A mutant) in complex with 8-oxo-dGTP

PDB ID 5gho

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