1vyq: Difference between revisions

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.

1VYQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum] with DUX as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1VYQ OCA].  

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