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

* Residue conservation analysis

PDB id:

3fkb

Name:

Transferase

Title:

Structure of ndpk h122g and tenofovir-diphosphate

Structure:

Nucleoside diphosphate kinase, cytosolic. Chain: a, b, c, d, e, f. Synonym: ndp kinase, ndk. Engineered: yes. Mutation: yes

Source:

Dictyostelium discoideum. Slime mold. Organism_taxid: 44689. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.65Å R-factor: 0.181 R-free: 0.205

Authors:

S.Morera,Y.X.Chen

Key ref:

K.Koch et al. (2009). 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. PubMed id: 20183617

Date:

16-Dec-08 Release date: 29-Sep-09

Protein chains

P22887  (NDKC_DICDI) -  Nucleoside diphosphate kinase, cytosolic from Dictyostelium discoideum

Seq: 155 a.a.

Struc: 150 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.7.4.6 - nucleoside-diphosphate kinase.
• Reaction:
  1. a ribonucleoside 5'-diphosphate + ATP = a ribonucleoside 5'-triphosphate + ADP
  2. a 2'-deoxyribonucleoside 5'-diphosphate + ATP = a 2'-deoxyribonucleoside 5'-triphosphate + ADP

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Nucleosides Nucleotides Nucleic Acids 28:776-792 (2009)

PubMed id: 20183617

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

K.Koch, Y.Chen, J.Y.Feng, K.Borroto-Esoda, D.Deville-Bonne, S.Gallois-Montbrun, J.Janin, S.Moréra.

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.