Deoxyuridine 5'-triphosphate nucleotidohydrolase

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{{STRUCTURE_1smc| PDB=1smc | SIZE=400| SCENE= |right|CAPTION= dUTPase trimer complex with dUTP, nitrate and Tris buffer [[1smc]] }}
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<StructureSection load='1w2y' size='350' side='right' caption='dUTPase complex with dUTP analog and Mg+2 ions (green) (PDB entry [[1w2y]])' scene='48/488500/Cv/1'>
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== Function ==
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'''Deoxyuridine 5’-triphosphate nucleotidohydrolase''' (DUTP) catalyzes the conversion of dUTP to dUMP and pyrophosphate (PPi). DUTP plays a key role in keeping significant amounts of dUTP from the DNA synthesis pathway. DUTP inhibitors are being tested as possible anti-bacterial agents targeting diseases like malaria, leishmaniasis, tuberculosis and trypanosomiasis. Prokaryotic DUTP contains metal ion.
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==3D structures of dUTPase==
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'''Deoxyuridine 5’-triphosphate nucleotidohydrolase''' or '''Deoxyuridine triphosphatase''' or '''dUTP pyrophosphatase''' (DUTP) catalyzes the conversion of dUTP to dUMP and pyrophosphate (PPi). DUTP plays a key role in keeping significant amounts of dUTP from the DNA synthesis pathway.
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Prokaryotic DUTP contains metal ion. <ref>PMID:18837522</ref>
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[[1dup]], [[1eu5]], [[1euw]] – EcDUTP – ''Escherichia coli''<br />
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== Relevance ==
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[[1dun]] – EvDUTP – Equine infectious anemia virus<br />
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[[1mq7]] – MtDUTP – ''Mycobacterium tuberculosis''<br />
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[[1ogl]] – TcDUTP – ''Trypanosoma cruzi''<br />
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[[2d4l]] - MPmvDUTP residues 83-234 – Mason_Pfizer monkey virus<br />
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[[2d4m]] - MPmvDUTP residues 83-234 (mutant) <br />
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[[2okb]], [[2okd]] - VvDUTP – Vaccinia virus<br />
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[[3hhq]] - yDUTP – yeast<br />
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[[3lqw]] - DUTP – ''Entamoeba histolytica''<br />
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[[3mbq]], [[3mdx]] - DUTP – ''Brucella melitensis''<br />
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[[2xx6]] - BsDUTP – ''Bacillus subtilis''<br />
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[[3tqz]] - DUTP – ''Coxiella burnetii''
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'''DUTP binary complexes'''
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DUTP inhibitors are being tested as possible anti-bacterial agents targeting diseases like malaria, leishmaniasis, tuberculosis and trypanosomiasis.
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[[1dud]] – EcDUTP + dUDP<br />
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== Structural highlights ==
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[[2hrm]] - EcDUTP + dUTP derivative<br />
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[[1seh]] - EcDUTP + dUMP<br />
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[[3f4f]] - yDUTP + dUMP<br />
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[[1dut]] – DUTP + Mg – Feline immunodeficiency virus<br />
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[[1ogk]] – TcDUTP + dUTP<br />
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[[1smc]] - MtDUTP + dUTP<br />
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[[1vyq]] - PfDUTP + inhibitor – ''Plasmodium falciparum''<br />
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[[2y8c]] - PfDUTP + trityl ligand<br />
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[[2bsy]], [[2we0]] - EbvDUTP + dUMP – Epstein-Barr virus<br />
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[[2we1]], [[2we2]] - EbvDUTP (mutant) + dUMP<br />
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[[2ol1]] - VvDUTP + dUMP<br />
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[[2y1t]] - BsDUTP + dUDP<br />
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[[2yb0]] - LmDUTP + dU – ''Leishmania major''<br />
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[[3tq5]], [[3trl]], [[3trn]], [[3ts6]], [[3tsl]], [[3tta]] - MPmvDUTP catalytic domain (mutant) + dUMP<br />
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'''DUTP ternary complexes'''
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The <scene name='48/488500/Cv/5'>active site</scene> contains Mg<sup>+2</sup> ions which are essensial for DUTP activity. The <scene name='48/488500/Cv/6'>Mg+2 ions are hexacoordinated to acidic residues and water molecules</scene>.<ref>PMID:15364583</ref> Water molecules are labeled Wa.
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==3D structures of dUTPase==
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[[dUTPase 3D structures]]
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[[1duc]] – EvDUPT + Sr + dUTP<br />
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</StructureSection>
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[[1six]], [[1sjn]], [[2py4]] – MtDUTP + Mg + dUTP derivative<br />
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[[3h6d]], [[3hza]], [[3i93]] - MtDUTP (mutant) + Mg + dUTP derivative<br />
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[[3loj]] - MtDUTP (mutant) + Mg + Mn + dUTP derivative<br />
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[[1rn8]] - EcDUTP + Mg + dUTP derivative<br />
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[[1rnj]] - EcDUTP (mutant) + Mg + dUTP derivative<br />
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[[1syl]] - EcDUTP (mutant) + Mg + dUTP<br />
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[[2hr6]] - EcDUTP + Mn + dUDP<br />
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[[1slh]] – MtDUTP + Mg + dUTP<br />
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[[1sm8]] – MtDUTP + Cr + dUTP<br />
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[[1snf]] - MtDUTP + Mg + dUMP<br />
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[[1w2y]], [[2cic]] - DUTP + Mg + dUTP derivative – ''Campylobacter jejuni''<br />
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[[2bt1]] - EbvDUTP + Mg + dUTP derivative<br />
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[[2we3]] - EbvDUTP residues 1-256 + Mg + dUTP<br />
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[[2d4n]] - MPmvDUTP residues 83-234 (mutant) + Mg + dUTP derivative<br />
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[[3tp1]] - MPmvDUTP catalytic domain + Mg + dUTP derivative<br />
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[[3tpw]], [[3tpn]], [[3tps]] - MPmvDUTP catalytic domain (mutant) + Mg + dUTP derivative<br />
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[[3tpy]], [[3tq3]], [[3tq4]] - MPmvDUTP catalytic domain + Mg + dUMP + dUTP derivative<br />
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[[2cje]] - LmDUTP + Mg + dUTP derivative<br />
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[[2yay]] - LmDUTP + Ca + dUTP derivative<br />
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[[2yaz]] - LmDUTP + Mg + dUMP<br />
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[[2oke]] - VvDUTP + Mg + dUTP derivative<br />
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[[2ol0]] - VvDUTP + Mg + dUDP<br />
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[[3c3i]] - PbcvDUTP (mutant) + Mg + dUDP – Paramecium bursaria chlorella virus<br />
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[[3c2t]], [[3ca9]] - PbcvDUTP + Mg + dUDP<br />
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[[2hqu]] - hDUTP + Mg + dUTP derivative – human<br />
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[[3ara]], [[3arn]] - hDUTP + Mg + uracil derivative<br />
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[[3p48]] - yDUTP + Mg + dUTP derivative<br />
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[[2xy3]] - BsDUTP + Mg + dUTP derivative<br />
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== References ==
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<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

dUTPase complex with dUTP analog and Mg+2 ions (green) (PDB entry 1w2y)

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References

  1. ↑ Vertessy BG, Toth J. Keeping uracil out of DNA: physiological role, structure and catalytic mechanism of dUTPases. Acc Chem Res. 2009 Jan 20;42(1):97-106. PMID:18837522 doi:10.1021/ar800114w
  2. ↑ Moroz OV, Harkiolaki M, Galperin MY, Vagin AA, Gonzalez-Pacanowska D, Wilson KS. The crystal structure of a complex of Campylobacter jejuni dUTPase with substrate analogue sheds light on the mechanism and suggests the "basic module" for dimeric d(C/U)TPases. J Mol Biol. 2004 Oct 1;342(5):1583-97. PMID:15364583 doi:10.1016/j.jmb.2004.07.050

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Michal Harel, Alexander Berchansky

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