View source for 3p48


==Structure of the yeast dUTPase DUT1 in complex with dUMPNPP==
<StructureSection load='3p48' size='340' side='right'caption='[[3p48]], [[Resolution|resolution]] 1.67&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.67&#8491;</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='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>
== 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.
<div style="background-color:#fffaf0;">
== 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<ref>PMID:21548881</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3p48" style="background-color:#fffaf0;"></div>

==See Also==
*[[DUTPase 3D structures|DUTPase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Edwards AM]]
[[Category: Evdokimova E]]
[[Category: Kudritska M]]
[[Category: Petit P]]
[[Category: Savchenko A]]
[[Category: Singer AU]]
[[Category: Yakunin AF]]