3fkb

From Proteopedia

Structure of NDPK H122G and tenofovir-diphosphate

Structural highlights

3fkb is a 6 chain structure with sequence from Dictyostelium discoideum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.65Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NDKC_DICDI

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

Nucleoside diphosphate kinase and the activation of antiviral phosphonate analogs of nucleotides: binding mode and phosphorylation of tenofovir derivatives.,Koch K, Chen Y, Feng JY, Borroto-Esoda K, Deville-Bonne D, Gallois-Montbrun S, Janin J, Morera S Nucleosides Nucleotides Nucleic Acids. 2009 Aug;28(8):776-92. PMID:20183617^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Koch K, Chen Y, Feng JY, 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. 2009 Aug;28(8):776-92. PMID:20183617 doi:10.1080/15257770903155899