View source for 1vyq


==Novel inhibitors of Plasmodium Falciparum dUTPase provide a platform for anti-malarial drug design==
<StructureSection load='1vyq' size='340' side='right'caption='[[1vyq]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1vyq]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VYQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1VYQ 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]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DUX:2,3-DEOXY-3-FLUORO-5-O-TRITYLURIDINE'>DUX</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=1vyq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vyq OCA], [https://pdbe.org/1vyq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1vyq RCSB], [https://www.ebi.ac.uk/pdbsum/1vyq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1vyq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q8II92_PLAF7 Q8II92_PLAF7] 
== 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/vy/1vyq_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=1vyq ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pyrimidine metabolism is a major route for therapeutic intervention against malaria. Here we report inhibition and structural studies on the deoxyuridine nucleotidohydrolase from the malaria parasite Plasmodium falciparum (PfdUTPase). We have identified a series of triphenylmethane derivatives of deoxyuridine with antimalarial activity in vitro which inhibit specifically the Plasmodium dUTPase versus the human enzyme. A 2.4 Angstrom crystal structure of PfdUTPase in complex with one of these inhibitors reveals an atypical trimeric enzyme in which the triphenylmethane derivative can be seen to select for PfdUTPase by way of interactions between the trityl group and the side chains of residues Phe46 and Ile117. Immunofluorescence microscopy studies of parasitized red blood cells reveal that enzyme concentrations are highest during the trophozoite/schizont stages, suggesting that PfdUTPase has a major role in DNA replication. Taken together the data show that PfdUTPase may be considered as an antimalarial drug target.

dUTPase as a platform for antimalarial drug design: structural basis for the selectivity of a class of nucleoside inhibitors.,Whittingham JL, Leal I, Nguyen C, Kasinathan G, Bell E, Jones AF, Berry C, Benito A, Turkenburg JP, Dodson EJ, Ruiz Perez LM, Wilkinson AJ, Johansson NG, Brun R, Gilbert IH, Gonzalez Pacanowska D, Wilson KS Structure. 2005 Feb;13(2):329-38. PMID:15698576<ref>PMID:15698576</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1vyq" style="background-color:#fffaf0;"></div>

==See Also==
*[[DUTPase 3D structures|DUTPase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum 3D7]]
[[Category: Bell E]]
[[Category: Benito A]]
[[Category: Berry C]]
[[Category: Brun R]]
[[Category: Dodson EJ]]
[[Category: Gilbert IH]]
[[Category: Gonzalez Pacanowska D]]
[[Category: Johansson NG]]
[[Category: Jones AF]]
[[Category: Kasinathan G]]
[[Category: Leal I]]
[[Category: Nguyen C]]
[[Category: Ruiz Perez LM]]
[[Category: Turkenburg JP]]
[[Category: Whittingham JL]]
[[Category: Wilkinson AJ]]
[[Category: Wilson KS]]