3FKB

Structure of NDPK H122G and tenofovir-diphosphate

Summary for 3FKB

• Entry DOI: 10.2210/pdb3fkb/pdb
• Related: 1b4s 1f3f 2bef
• Descriptor: Nucleoside diphosphate kinase, cytosolic, [(2R)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethyl-phosphonooxy-phosphinic acid, MAGNESIUM ION, ... (7 entities in total)
• Functional Keywords: an hexamer structure, atp-binding, kinase, magnesium, metal-binding, nucleotide metabolism, nucleotide-binding, phosphoprotein, transferase
• Biological source: Dictyostelium discoideum (Slime mold)
• Cellular location: Cytoplasm: P22887
• Total number of polymer chains: 6
• Total formula weight: 103334.94

Authors

Morera, S.,Chen, Y.X. (deposition date: 2008-12-16, release date: 2009-09-29, Last modification date: 2023-11-01)

Primary citation

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

PubMed 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.

PubMed: 20183617
DOI: 10.1080/15257770903155899

Experimental method

X-RAY DIFFRACTION (1.65 Å)