Insight into the mechanism of inactivation of ribonucleotide reductase by gemcitabine 5'-diphosphate in the presence or absence of reductant.

@article{Artin2009InsightIT,
  title={Insight into the mechanism of inactivation of ribonucleotide reductase by gemcitabine 5'-diphosphate in the presence or absence of reductant.},
  author={Erin Jelena Artin and Jun Rong Wang and Gregory J S Lohman and Kenichi Yokoyama and Guixue Yu and Robert G Griffin and Galit Bar and Joanne Stubbe},
  journal={Biochemistry},
  year={2009},
  volume={48 49},
  pages={11622-9}
}
Gemcitabine 5'-diphosphate (F(2)CDP) is a potent inhibitor of ribonucleotide reductases (RNRs), enzymes that convert nucleotides (NDPs) to deoxynucleotides and are essential for DNA replication and repair. The Escherichia coli RNR, an alpha2beta2 complex, when incubated with 1 equiv of F(2)CDP catalyzes the release of two fluorides and cytosine concomitant with enzyme inactivation. In the presence of reductant (thioredoxin/thioredoxin reductase/NADPH or DTT), the enzyme inactivation results… CONTINUE READING