The exceptional properties of Plasmodium deoxyguanylate pathways as a potential area for metabolic and drug discovery studies.
In Plasmodium falciparum, deoxyguanylate was found to be a substrate for several DNA metabolizing enzymes. Guanylate kinase utilizes dGMP with very low specificity, which is estimated to be the lowest among well-known prokaryotic and eukaryotic enzymes. Furthermore, thymidylate kinase, which is a pyrimidine specific enzyme, was found to phosphorylate dGMP with a surprisingly high specificity similar to that of the natural substrate. The above mentioned distinctions are specific for the Plasmodium protozoa and provide an interesting method for tracking dGMP metabolism during development and a starting point for drug development.
Kandeel
Mahmoud
M
Department of Biomolecular Science, Faculty of Engineering, Center for Advanced Drug Research and Center for Emerging Infectious Diseases and United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu 501-1193, Japan.
Kitamura
Yoshiaki
Y
Kitade
Yukio
Y
D000818:Animals; D003848:Deoxyguanine Nucleotides / Q000378:metabolism*; D055808:Drug Discovery; D051528:Guanylate Kinases / Q000378:metabolism*; D006801:Humans; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000201:enzymology*
D003848:Deoxyguanine Nucleotides; C007257:2'-deoxyguanosine 5'-phosphate; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases; C020093:dTMP kinase