Journal
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
Volume 173, Issue 2, Pages 165-169Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molbiopara.2010.05.018
Keywords
Plasmodium vivax; Purine salvage pathway; 6-Oxopurine phosphoribosyltransferase; Acyclic nucleoside phosphonates
Categories
Funding
- National Health and Medical Research Council, Australia [569703]
- Institute of Organic Chemistry and Biochemistry [AVOZ40550506]
- Centre for New Antivirals and Antineoplastics [1M0508]
Ask authors/readers for more resources
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 K-i values as low as 3 mu M. These compounds can form the basis for the design of new drugs aimed at combating malaria caused by Pv. (C) 2010 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available