Title: Plasmodium vivax hypoxanthine-guanine phosphoribosyltransferase: a target for anti-malarial chemotherapy
Authors: Keough, Dianne T ×
Hocková, Dana
Krecmerová, Marcela
Cesnek, Michal
Holý, Antonín
Naesens, Lieve
Brereton, Ian M
Winzor, Donald J
de Jersey, John
Guddat, Luke W #
Issue Date: Oct-2010
Publisher: Elsevier/North-Holland Biomedical Press
Series Title: Molecular and Biochemical Parasitology vol:173 issue:2 pages:165-9
Abstract: The malarial parasite, Plasmodium vivax (Pv), causes a serious infectious disease found primarily in Asia and the Americas. For protozoan parasites, 6-oxopurine phosphoribosyltransferases (PRTases) provide the only metabolic pathway to synthesize the purine nucleoside monophosphates essential for DNA/RNA production. We have purified the recombinant Pv 6-oxopurine (PRTase) and compared its properties with the human and Pf enzymes. The Pv enzyme uses hypoxanthine and guanine with similar catalytic efficiency to the Pf enzyme but xanthine is not a substrate, hence we identify this enzyme as PvHGPRT. Mass spectrometry suggests that PvHGPRT contains bound magnesium ions that are removed by EDTA resulting in loss of activity. However, the addition of Mg(2+) restores activity. Acyclic nucleoside phosphonates (ANPs) are good inhibitors of PvHGPRT having K(i) values as low as 3 microM. These compounds can form the basis for the design of new drugs aimed at combating malaria caused by Pv.
ISSN: 0166-6851
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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