View source for 2we0


==EBV dUTPase mutant Cys4Ser==
<StructureSection load='2we0' size='340' side='right'caption='[[2we0]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2we0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_herpesvirus_4_strain_B95-8 Human herpesvirus 4 strain B95-8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WE0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WE0 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]] 2.01&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TEO:MALATE+LIKE+INTERMEDIATE'>TEO</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</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=2we0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2we0 OCA], [https://pdbe.org/2we0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2we0 RCSB], [https://www.ebi.ac.uk/pdbsum/2we0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2we0 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DUT_EBVB9 DUT_EBVB9] Involved in nucleotide metabolism: produces dUMP, the immediate precursor of thymidine nucleotides and decreases the intracellular concentration of dUTP to avoid uracil incorporation into DNA. Induces immune dysregulation that contributes to the pathophysiology of the virus infection.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/we/2we0_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2we0 ConSurf].
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== Publication Abstract from PubMed ==
Deoxyuridine 5'-triphosphate pyrophosphatases (dUTPases) are ubiquitous enzymes essential for hydrolysis of dUTP, thus preventing its incorporation into DNA. Although Epstein-Barr virus (EBV) dUTPase is monomeric, it has a high degree of similarity with the more frequent trimeric form of the enzyme. In both cases, the active site is composed of five conserved sequence motifs. Structural and functional studies of mutants based on the structure of EBV dUTPase gave new insight into the mechanism of the enzyme. A first mutant allowed us to exclude a role in enzymatic activity for the disulfide bridge involving the beginning of the disordered C terminus. Sequence alignments revealed two groups of dUTPases, based on the position in sequence of a conserved aspartic acid residue close to the active site. Single mutants of this residue in EBV dUTPase showed a highly impaired catalytic activity, which could be partially restored by a second mutation, making EBV dUTPase more similar to the second group of enzymes. Deletion of the flexible C-terminal tail carrying motif V resulted in a protein completely devoid of enzymatic activity, crystallizing with unhydrolyzed Mg(2+)-dUTP complex in the active site. Point mutations inside motif V highlighted the essential role of lid residue Phe(273). Magnesium appears to play a role mainly in substrate binding, since in absence of Mg(2+), the K(m) of the enzyme is reduced, whereas the k(cat) is less affected.

The flexible motif V of Epstein-Barr virus deoxyuridine 5'-triphosphate pyrophosphatase is essential for catalysis.,Freeman L, Buisson M, Tarbouriech N, Van der Heyden A, Labbe P, Burmeister WP J Biol Chem. 2009 Sep 11;284(37):25280-9. Epub 2009 Jul 7. PMID:19586911<ref>PMID:19586911</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[DUTPase 3D structures|DUTPase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human herpesvirus 4 strain B95-8]]
[[Category: Large Structures]]
[[Category: Buisson M]]
[[Category: Burmeister WP]]
[[Category: Freeman L]]
[[Category: Tarbouriech N]]