7,8-dihydro-8-oxoguanine triphosphatase

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<StructureSection load='3zr0' size='350' side='right' caption='Structure of human MTH1 complex with 8-oxo-dGTP (stick model) and sulfate (PDB code [[3zr0]]).' scene='59/597008/Cv/1'>
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<StructureSection load='3zr0' size='350' side='right' caption='Structure of human MTH1 complex with 8-oxo-dGTP and sulfate (PDB code [[3zr0]]).' scene='59/597008/Cv/1'>
== Function ==
== Function ==
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'''7,8-dihydro-8-oxoguanine triphosphatase''' (DGTP) converts 8-oxoguanine containing deoxyribonucleoside triphosphate to the corresponding monophosphate. DGTP controls spontaneous mutagenesis caused by exogenous oxygen radicals. The ''E. coli'' DGTP is called '''MutT'''. The human DGTP is called '''MTH1'''.<ref>PMID:19864691</ref>
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'''7,8-dihydro-8-oxoguanine triphosphatase''' (DGTP) converts 8-oxoguanine containing deoxyribonucleoside triphosphate to the corresponding monophosphate. DGTP controls spontaneous mutagenesis caused by exogenous oxygen radicals.<br/ >
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The ''E. coli'' DGTP is called '''MutT'''. <ref>PMID:1309939</ref> <br />
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The human DGTP is called '''MTH1'''.<ref>PMID:19864691</ref>
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For details on MTH1 see [[Student Project 7 for UMass Chemistry 423 Spring 2015]].
== Relevance ==
== Relevance ==
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The 8-oxo-dGTP (oxoG) is a potentially mutagenic substrate when incorporated into DNA.
The 8-oxo-dGTP (oxoG) is a potentially mutagenic substrate when incorporated into DNA.
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</StructureSection>
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== Structural highlights ==
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*<scene name='59/597008/Cv/5'>Active site</scene> of DGTP (PDB code [[3zr0]]).<ref>PMID:21787772</ref> Water molecules are shown as red spheres.
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*<scene name='59/597008/Cv/6'>8-oxo-dGTP is located in the tunnel</scene>.
==3D structures of 7,8-dihydro-8-oxoguanine triphosphatase==
==3D structures of 7,8-dihydro-8-oxoguanine triphosphatase==
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[[7,8-dihydro-8-oxoguanine triphosphatase 3D structures]]
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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</StructureSection>
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*DGTP
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**[[4jzs]] – BsDGTP (mutant) – ''Bacillus subtilis''<br />
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**[[4jzt]] – BsDGTP (mutant) + GTP <br />
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**[[4jzu]], [[4jzv]] – BsDGTP + RNA triphosphorylated<br />
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*MutT
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**[[3a6s]] – EcMutT – ''Escherichia coli'' <br />
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**[[1mut]] – EcMutT - NMR<br />
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**[[3a6v]] – EcMutT + Mn<br />
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**[[1tum]] – EcMutT + Mg + ATP derivative - NMR<br />
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**[[3a6t]] – EcMutT + oxoG <br />
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**[[3a6u]] – EcMutT + Mn + oxoG <br />
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**[[1ppx]], [[1pun]], [[1puq]], [[1pus]] – EcMutT + Mg + oxoG - NMR<br />
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*MTH1
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**[[3q93]], [[3zr1]] – hMTH1 - human <br />
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**[[1iry]] – hMTH1 - NMR<br />
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**[[3zr0]] – hMTH1 + oxoG<br />
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**[[3whw]], [[4n1t]], [[4n1u]] – hMTH1 + inhibitor<br />
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**[[4c9w]], [[4c9x]] – hMTH1 + anti-cancer drug<br />
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}}
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== References ==
== References ==

Current revision

Structure of human MTH1 complex with 8-oxo-dGTP and sulfate (PDB code 3zr0).

Drag the structure with the mouse to rotate

References

  1. ↑ Maki H, Sekiguchi M. MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis. Nature. 1992 Jan 16;355(6357):273-5. PMID:1309939 doi:http://dx.doi.org/10.1038/355273a0
  2. ↑ Nakamura T, Meshitsuka S, Kitagawa S, Abe N, Yamada J, Ishino T, Nakano H, Tsuzuki T, Doi T, Kobayashi Y, Fujii S, Sekiguchi M, Yamagata Y. Structural and dynamic features of the MutT protein in the recognition of nucleotides with the mutagenic 8-oxoguanine base. J Biol Chem. 2010 Jan 1;285(1):444-52. Epub 2009 Oct 28. PMID:19864691 doi:10.1074/jbc.M109.066373
  3. ↑ Svensson LM, Jemth AS, Desroses M, Loseva O, Helleday T, Hogbom M, Stenmark P. Crystal structure of human MTH1 and the 8-oxo-dGMP product complex. FEBS Lett. 2011 Aug 19;585(16):2617-21. Epub 2011 Jul 23. PMID:21787772 doi:10.1016/j.febslet.2011.07.017

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