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| | <StructureSection load='3p48' size='340' side='right'caption='[[3p48]], [[Resolution|resolution]] 1.67Å' scene=''> | | <StructureSection load='3p48' size='340' side='right'caption='[[3p48]], [[Resolution|resolution]] 1.67Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3p48]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P48 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P48 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3p48]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P48 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P48 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DUP:2-DEOXYURIDINE+5-ALPHA,BETA-IMIDO-TRIPHOSPHATE'>DUP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.67Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3f4f|3f4f]], [[3hhq|3hhq]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DUP:2-DEOXYURIDINE+5-ALPHA,BETA-IMIDO-TRIPHOSPHATE'>DUP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DUT1, YBR252W, YBR1705 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/dUTP_diphosphatase dUTP diphosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.23 3.6.1.23] </span></td></tr>
| + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3p48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p48 OCA], [https://pdbe.org/3p48 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p48 RCSB], [https://www.ebi.ac.uk/pdbsum/3p48 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p48 ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3p48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p48 OCA], [https://pdbe.org/3p48 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p48 RCSB], [https://www.ebi.ac.uk/pdbsum/3p48 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p48 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DUT_YEAST DUT_YEAST]] This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.
| + | [https://www.uniprot.org/uniprot/DUT_YEAST DUT_YEAST] This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 18824]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: DUTP diphosphatase]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Edwards, A M]] | + | [[Category: Edwards AM]] |
| - | [[Category: Evdokimova, E]] | + | [[Category: Evdokimova E]] |
| - | [[Category: Kudritska, M]] | + | [[Category: Kudritska M]] |
| - | [[Category: OCSP, Ontario Centre for Structural Proteomics]]
| + | [[Category: Petit P]] |
| - | [[Category: Petit, P]] | + | [[Category: Savchenko A]] |
| - | [[Category: Savchenko, A]] | + | [[Category: Singer AU]] |
| - | [[Category: Singer, A U]] | + | [[Category: Yakunin AF]] |
| - | [[Category: Yakunin, A F]] | + | |
| - | [[Category: Beta barrel]]
| + | |
| - | [[Category: Dumppnp pyrophosphatase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Ocsp]]
| + | |
| - | [[Category: Ontario centre for structural proteomic]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Structural genomic]]
| + | |
| - | [[Category: Trimer]]
| + | |
| Structural highlights
Function
DUT_YEAST This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.
Publication Abstract from PubMed
Genomes of all free-living organisms encode the enzyme dUTPase (dUTP pyrophosphatase), which plays a key role in preventing uracil incorporation into DNA. In the present paper, we describe the biochemical and structural characterization of DUT1 (Saccharomyces cerevisiae dUTPase). The hydrolysis of dUTP by DUT1 was strictly dependent on a bivalent metal cation with significant activity observed in the presence of Mg2+, Co2+, Mn2+, Ni2+ or Zn2+. In addition, DUT1 showed a significant activity against another potentially mutagenic nucleotide: dITP. With both substrates, DUT1 demonstrated a sigmoidal saturation curve, suggesting a positive co-operativity between the subunits. The crystal structure of DUT1 was solved at 2 A resolution (1 A=0.1 nm) in an apo state and in complex with the non-hydrolysable substrate alpha,beta-imido dUTP or dUMP product. Alanine-replacement mutagenesis of the active-site residues revealed seven residues important for activity including the conserved triad Asp87/Arg137/Asp85. The Y88A mutant protein was equally active against both dUTP and UTP, indicating that this conserved tyrosine residue is responsible for discrimination against ribonucleotides. The structure of DUT1 and site-directed mutagenesis support a role of the conserved Phe142 in the interaction with the uracil base. Our work provides further insight into the molecular mechanisms of substrate selectivity and catalysis of dUTPases.
Structure and activity of the Saccharomyces cerevisiae dUTP pyrophosphatase DUT1, an essential housekeeping enzyme.,Tchigvintsev A, Singer AU, Flick R, Petit P, Brown G, Evdokimova E, Savchenko A, Yakunin AF Biochem J. 2011 Jul 15;437(2):243-53. PMID:21548881[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tchigvintsev A, Singer AU, Flick R, Petit P, Brown G, Evdokimova E, Savchenko A, Yakunin AF. Structure and activity of the Saccharomyces cerevisiae dUTP pyrophosphatase DUT1, an essential housekeeping enzyme. Biochem J. 2011 Jul 15;437(2):243-53. PMID:21548881 doi:http://dx.doi.org/10.1042/BJ20110304
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