Human ribonucleotide reductase. Activation and inhibition by analogs of ATP.
Sixteen ATP analogs were studied as activators of CDP reduction catalyzed by human ribonucleotide reductase. Activation constants were determined. Three analogs, 3-deazaATP, 5'-adenylimidodiphosphate, and 3'-dATP, activated approximately as efficiently as ATP. Four analogs were partial activators. These seven activators were also accessory activators of GDP reduction. Furthermore, two other analogs, adenosine-5'-O-(1-thiotriphosphate) and 8-bromoATP, selectively stimulated GDP reduction. Ten analogs, at equal molar concentrations with ATP, inhibited ATP-dependent activation of CDP reduction and/or accessory activation of GDP reduction by greater than 45%. No analog inhibited as potently as 2'-dATP, which had an IC50 of 30-50 microM versus the stimulation of CDP and GDP reduction by 2.0 mM ATP.
Harrington
J A
JA
Burroughs Wellcome Co., Wellcome Research Laboratories, Research Triangle Park, NC 27709.
Spector
T
T
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003565:Cytidine Diphosphate / Q000378:metabolism; D004789:Enzyme Activation; D006153:Guanosine Diphosphate / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D006153:Guanosine Diphosphate; D003565:Cytidine Diphosphate; D000255:Adenosine Triphosphate; D012264:Ribonucleotide Reductases