In vitro generation of ribonucleotide reductase with altered sensitivity to the inhibitors hydroxyurea and deoxynucleoside triphosphates

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Abstract
Modified preparations of [mouse] Ehrlich-tumor-cell ribonucleotide reductase were generated by adding either exogenous non-heme iron-containing (NHI) component or effector-binding (EB) component to the partially purified enzyme. The modified enzymes showed altered sensitivity to the negative effectors dATP, dTTP and dGTP and to hydroxyurea. In the preparation with excess NHI component the sensitivity to these compounds was decreased, while, conversely, in the preparations with excess EB fraction there was increased sensitivity to these compounds. These data may explain the molecular basis for the mutant forms of ribonucleotide reductase that have been reported.