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Nucleosides Nucleotides Nucleic Acids. 2009 Aug;28(8):776-92. doi: 10.1080/15257770903155899.

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

Author information

1
Yeast Structural Genomics, IBBMC UMR 8619 CNRS, Universite Paris-Sud, Orsay, France.

Erratum in

  • Nucleosides Nucleotides Nucleic Acids. 2009 Oct;28(10):987. Gallois-Montbrun, Sarah [added].

Abstract

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 subset of the Van der Waals and polar interactions made by natural substrates, consistent with their comparatively low affinity for the enzyme.

PMID:
20183617
DOI:
10.1080/15257770903155899
[Indexed for MEDLINE]

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