The enantioselectivities of the active and allosteric sites of mammalian ribonucleotide reductase.

Here we examine the enantioselectivity of the allosteric and substrate binding sites of murine ribonucleotide reductase (mRR). L-ADP binds to the active site and L-ATP binds to both the s- and a-allosteric sites of mR1 with affinities that are only three- to 10-fold weaker than the values for the corresponding D-enantiomers. These results demonstrate the potential of L-nucleotides for interacting with and modulating the activity of mRR, a cancer chemotherapeutic and antiviral target. On the other hand, we detect no substrate activity for L-ADP and no inhibitory activity for N3-L-dUDP, demonstrating the greater stereochemical stringency at the active site with respect to catalytic activity.