PDBsum entry 3fkb

Transferase

PDB id: 3fkb

Contents

Protein chains

(+ 0 more) 150 a.a.

Ligands

TNM ×5

EDO ×5

GOL ×2

TNV

Metals

_MG ×6

Waters ×1278

References listed in PDB file

Key reference

• Title: Nucleoside diphosphate kinase and the activation of antiviral phosphonate analogs of nucleotides: binding mode and phosphorylation of tenofovir derivatives.
• Authors: K.Koch, Y.Chen, J.Y.Feng, K.Borroto-Esoda, D.Deville-Bonne, S.Gallois-Montbrun, J.Janin, S.Moréra.
• Ref.: Nucleosides Nucleotides Nucleic Acids, 2009, 28, 776-792.
• PubMed id: 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.