title: Human ribonucleotide reductase. Activation and inhibition by analogs of ATP.
abstract: 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.
authors.affiliation: Burroughs Wellcome Co., Wellcome Research Laboratories, Research Triangle Park, NC 27709.
authors.forename: J A
authors.initials: JA
authors.lastname: Harrington
authors.forename: T
authors.initials: T
authors.lastname: Spector
mesh_terms: 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*
chemical_list: D006153:Guanosine Diphosphate; D003565:Cytidine Diphosphate; D000255:Adenosine Triphosphate; D012264:Ribonucleotide Reductases