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8i8t

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'''Unreleased structure'''
 
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The entry 8i8t is ON HOLD until Paper Publication
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==Crystal structure of human MTH1(G2K mutant) in complex with 2-oxo-dAMP and Mn2+==
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<StructureSection load='8i8t' size='340' side='right'caption='[[8i8t]], [[Resolution|resolution]] 1.22&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8i8t]] 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=8I8T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8I8T 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]] 1.22&#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=IGU:2-DEOXYISOGUANINE-5-MONOPHOSPHATE'>IGU</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=8i8t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8i8t OCA], [https://pdbe.org/8i8t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8i8t RCSB], [https://www.ebi.ac.uk/pdbsum/8i8t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8i8t 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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Human MutT homolog 1 (MTH1), also known as Nudix-type motif 1 (NUDT1), hydrolyzes 8-oxo-dGTP and 2-oxo-dATP with broad substrate recognition and has attracted attention in anticancer therapeutics. Previous studies on MTH1 have proposed that the exchange of the protonation state between Asp119 and Asp120 is essential for the broad substrate recognition of MTH1. To understand the relationship between protonation states and substrate binding, we determined the crystal structures of MTH1 at pH 7.7-9.7. With increasing pH, MTH1 gradually loses its substrate-binding ability, indicating that Asp119 is deprotonated at pH 8.0-9.1 in 8-oxo-dGTP recognition and Asp120 is deprotonated at pH 8.6-9.7 in 2-oxo-dATP recognition. These results confirm that MTH1 recognizes 8-oxo-dGTP and 2-oxo-dATP by exchanging the protonation state between Asp119 and Asp120 with higher pK(a) .
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Authors:
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Protonation states of Asp residues in the human Nudix hydrolase MTH1 contribute to its broad substrate recognition.,Nakamura T, Koga-Ogawa Y, Fujimiya K, Chirifu M, Goto M, Ikemizu S, Nakabeppu Y, Yamagata Y FEBS Lett. 2023 Jul;597(13):1770-1778. doi: 10.1002/1873-3468.14611. Epub 2023 , Mar 23. PMID:36914375<ref>PMID:36914375</ref>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 8i8t" style="background-color:#fffaf0;"></div>
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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: Nakamura T]]
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[[Category: Yamagata Y]]

Current revision

Crystal structure of human MTH1(G2K mutant) in complex with 2-oxo-dAMP and Mn2+

PDB ID 8i8t

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