1vyq
From Proteopedia
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|SITE= <scene name='pdbsite=AC1:Dux+Binding+Site+For+Chain+A'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Dux+Binding+Site+For+Chain+A'>AC1</scene> | ||
|LIGAND= <scene name='pdbligand=DUX:2,3-DEOXY-3-FLUORO-5-O-TRITYLURIDINE'>DUX</scene> | |LIGAND= <scene name='pdbligand=DUX:2,3-DEOXY-3-FLUORO-5-O-TRITYLURIDINE'>DUX</scene> | ||
| - | |ACTIVITY= [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] | + | |ACTIVITY= <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> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<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://www.ebi.ac.uk/pdbsum/1vyq PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1vyq RCSB]</span> | ||
}} | }} | ||
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[[Category: Wilkinson, A J.]] | [[Category: Wilkinson, A J.]] | ||
[[Category: Wilson, K S.]] | [[Category: Wilson, K S.]] | ||
| - | [[Category: DUX]] | ||
[[Category: deoxyuridine nucleotidohydrolase]] | [[Category: deoxyuridine nucleotidohydrolase]] | ||
[[Category: drug design]] | [[Category: drug design]] | ||
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[[Category: plasmodium falciparum]] | [[Category: plasmodium falciparum]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:28:52 2008'' |
Revision as of 21:28, 30 March 2008
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| , resolution 2.4Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | |||||||
| Activity: | dUTP diphosphatase, with EC number 3.6.1.23 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
NOVEL INHIBITORS OF PLASMODIUM FALCIPARUM DUTPASE PROVIDE A PLATFORM FOR ANTI-MALARIAL DRUG DESIGN
Overview
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.
About this Structure
1VYQ is a Single protein structure of sequence from Plasmodium falciparum. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Mon Mar 31 00:28:52 2008
Categories: Plasmodium falciparum | Single protein | DUTP diphosphatase | Bell, E. | Benito, A. | Berry, C. | Brun, R. | Dodson, E J. | Gilbert, I H. | Johansson, N G. | Jones, A F. | Kasinathan, G. | Leal, I. | Nguyen, C. | Pacanowska, D Gonzalez. | Perez, L M.Ruiz. | Turkenburg, J P. | Whittingham, J L. | Wilkinson, A J. | Wilson, K S. | Deoxyuridine nucleotidohydrolase | Drug design | Dutpase | Hydrolase | Malaria
