Nucleoside diphosphate kinase and the activation of antiviral phosphonate analogs of nucleotides: binding mode and phosphorylation of tenofovir derivatives.

@article{Koch2009NucleosideDK,
  title={Nucleoside diphosphate kinase and the activation of antiviral phosphonate analogs of nucleotides: binding mode and phosphorylation of tenofovir derivatives.},
  author={Kerstin Koch and Yuxing Chen and Joy Y Feng and Katyna Borroto-Esoda and Dominique Deville-Bonne and Sarah Gallois-Montbrun and Jo{\"e}l Janin and Solange Mor{\'e}ra},
  journal={Nucleosides, nucleotides & nucleic acids},
  year={2009},
  volume={28 8},
  pages={776-92}
}
Tenofovir is an acyclic phosphonate analog of deoxyadenylate used in AIDS and hepatitis B therapy. We find that tenofovir diphosphate, its active form, can be produced by human nucleoside diphosphate kinase (NDPK), but with low efficiency, and that creatine kinase is significantly more active. The 1.65 A x-ray structure of NDPK in complex with tenofovir mono- and diphosphate shows that the analogs bind at the same site as natural nucleotides, but in a different conformation, and make only a… CONTINUE READING