Inhibition of CTP synthase from Escherichia coli by xanthines and uric acids.
CTP synthase (CTPS) catalyzes the conversion of UTP to CTP and is a recognized target for the development of anticancer, antiviral, and antiprotozoal agents. Xanthine and related compounds inhibit CTPS activity (IC(50)=0.16-0.58mM). The presence of an 8-oxo function (i.e., uric acids) enhances inhibition (IC(50)=0.060-0.121mM). An intact purine ring with anionic character favors inhibition. In general, methylation of the purine does not significantly affect inhibition.
Roy
Alexander C
AC
Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 1X5.
Lunn
Faylene A
FA
Bearne
Stephen L
SL
D019731:Carbon-Nitrogen Ligases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology*; D007700:Kinetics; D008745:Methylation; D013329:Structure-Activity Relationship; D014527:Uric Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014970:Xanthines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014970:Xanthines; D014527:Uric Acid; D019731:Carbon-Nitrogen Ligases; C019951:CTP synthetase