Plasmodium vivax hypoxanthine-guanine phosphoribosyltransferase: A target for anti-malarial chemotherapy

Keough, Dianne T., Hockova, Daná, Krečmerová, Marcela, Česnek, Michal, Holý, Antonín, Naesens, Lieve, Brereton, Ian M., Winzor, Donald J., de Jersey, John and Guddat, Luke W. (2010) Plasmodium vivax hypoxanthine-guanine phosphoribosyltransferase: A target for anti-malarial chemotherapy. Molecular and Biochemical Parasitology, 173 2: 165-169. doi:10.1016/j.molbiopara.2010.05.018


Author Keough, Dianne T.
Hockova, Daná
Krečmerová, Marcela
Česnek, Michal
Holý, Antonín
Naesens, Lieve
Brereton, Ian M.
Winzor, Donald J.
de Jersey, John
Guddat, Luke W.
Title Plasmodium vivax hypoxanthine-guanine phosphoribosyltransferase: A target for anti-malarial chemotherapy
Journal name Molecular and Biochemical Parasitology   Check publisher's open access policy
ISSN 0166-6851
1872-9428
Publication date 2010-10
Sub-type Article (original research)
DOI 10.1016/j.molbiopara.2010.05.018
Volume 173
Issue 2
Start page 165
End page 169
Total pages 5
Editor P. T. LoVerde
K. R. Matthews
M. Parsons
A. P. Waters
Place of publication Amsterdam, Netherlands
Publisher Elsevier/North Holland
Collection year 2011
Language eng
Formatted 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 Mg2+ restores activity. Acyclic nucleoside phosphonates (ANPs) are good inhibitors of PvHGPRT having Ki values as low as 3 μM. These compounds can form the basis for the design of new drugs aimed at combating malaria caused by Pv.
© 2010 Elsevier B.V. All rights reserved.
Keyword Plasmodium vivax
Purine salvage pathway
6-oxopurine phosphoribosyltransferase
Acyclic nucleoside phosphonates
Human malaria parasite
Xanthine phosphoribosyltransferase
Falciparum
Analogs
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Chemistry and Molecular Biosciences
Centre for Advanced Imaging Publications
 
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Created: Sun, 22 Aug 2010, 00:05:51 EST