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1vyq

From Proteopedia

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Current revision

Novel inhibitors of Plasmodium Falciparum dUTPase provide a platform for anti-malarial drug design

Structural highlights

1vyq is a 3 chain structure with sequence from Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q8II92_PLAF7

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. dUTPase as a platform for antimalarial drug design: structural basis for the selectivity of a class of nucleoside inhibitors. Structure. 2005 Feb;13(2):329-38. PMID:15698576 doi:10.1016/j.str.2004.11.015

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1vyq"

@@ Line 3: / Line 3: @@
 <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 [http://en.wikipedia.org/wiki/Plaf7 Plaf7]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1VYQ FirstGlance]. <br>
+<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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DUX:2,3-DEOXY-3-FLUORO-5-O-TRITYLURIDINE'>DUX</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]] 2.4&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/dUTP_diphosphatase dUTP diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.23 3.6.1.23] </span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1vyq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vyq OCA], [http://pdbe.org/1vyq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1vyq RCSB], [http://www.ebi.ac.uk/pdbsum/1vyq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1vyq 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=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]]
@@ Line 35: / Line 37: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Plaf7]]
+[[Category: Plasmodium falciparum 3D7]]
-[[Category: DUTP diphosphatase]]
+[[Category: Bell E]]
-[[Category: Bell, E]]
+[[Category: Benito A]]
-[[Category: Benito, A]]
+[[Category: Berry C]]
-[[Category: Berry, C]]
+[[Category: Brun R]]
-[[Category: Brun, R]]
+[[Category: Dodson EJ]]
-[[Category: Dodson, E J]]
+[[Category: Gilbert IH]]
-[[Category: Gilbert, I H]]
+[[Category: Gonzalez Pacanowska D]]
-[[Category: Johansson, N G]]
+[[Category: Johansson NG]]
-[[Category: Jones, A F]]
+[[Category: Jones AF]]
-[[Category: Kasinathan, G]]
+[[Category: Kasinathan G]]
-[[Category: Leal, I]]
+[[Category: Leal I]]
-[[Category: Nguyen, C]]
+[[Category: Nguyen C]]
-[[Category: Pacanowska, D Gonzalez]]
+[[Category: Ruiz Perez LM]]
-[[Category: Perez, L M.Ruiz]]
+[[Category: Turkenburg JP]]
-[[Category: Turkenburg, J P]]
+[[Category: Whittingham JL]]
-[[Category: Whittingham, J L]]
+[[Category: Wilkinson AJ]]
-[[Category: Wilkinson, A J]]
+[[Category: Wilson KS]]
-[[Category: Wilson, K S]]
-[[Category: Deoxyuridine nucleotidohydrolase]]
-[[Category: Drug design]]
-[[Category: Dutpase]]
-[[Category: Hydrolase]]
-[[Category: Malaria]]
-[[Category: Plasmodium falciparum]]

1vyq

From Proteopedia

Current revision

Novel inhibitors of Plasmodium Falciparum dUTPase provide a platform for anti-malarial drug design

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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