Nucleoside diphosphate kinase and the activation of antiviral phosphonate analogs of nucleotides: binding mode and phosphorylation of tenofovir derivatives.
Nucleosides Nucleotides Nucleic Acids
; 28(8): 776-92, 2009 Aug.
Article
em En
| MEDLINE
| ID: mdl-20183617
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Adenina
/
Núcleosídeo-Difosfato Quinase
/
Organofosfonatos
/
Nucleotídeos
Limite:
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article