1vyq

From Proteopedia

Revision as of 07:44, 30 October 2007

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 ... [(full description)]

About this Structure

1VYQ is a [Single protein] structure of sequence from [Plasmodium falciparum] with DUX as [ligand]. Active as [Hydrolase], with EC number [3.6.1.23]. Structure known Active Site: AC1. 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

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