This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

1vyq

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 07:44, 4 April 2018

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 Plaf7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Activity:	dUTP diphosphatase, with EC number 3.6.1.23
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 Evolutionary Conservation
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
-==NOVEL INHIBITORS OF PLASMODIUM FALCIPARUM DUTPASE PROVIDE A PLATFORM FOR ANTI-MALARIAL DRUG DESIGN==
+==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 ==
@@ Line 5: / Line 6: @@
 </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>
 <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='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]</span></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>
 </table>
 == Evolutionary Conservation ==
@@ Line 11: / Line 12: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vy/1vyq_consurf.spt"</scriptWhenChecked>
+    <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>

1vyq

From Proteopedia

Revision as of 07:44, 4 April 2018

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

Structural highlights

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox