2VP0

Structural Studies of Nucleoside Analog and Feedback Inhibitor Binding to Drosophila Melanogaster Multisubstrate Deoxyribonucleoside Kinase

Summary for 2VP0

• Entry DOI: 10.2210/pdb2vp0/pdb
• Related: 1J90 1OE0 1OT3 1ZM7 1ZMX 2JCS
• Descriptor: DEOXYNUCLEOSIDE KINASE, MAGNESIUM ION, THYMIDINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: atp-binding, dna synthesis, phosphoprotein, feedback inhibition, deoxyribonucleoside kinase, salvage pathway, nucleotide-binding, dttp, kinase, complex, drosophila, transferase
• Biological source: DROSOPHILA MELANOGASTER (FRUIT FLY)
• Total number of polymer chains: 2
• Total formula weight: 59267.45

Authors

Mikkelsen, N.E.,Munch-Petersen, B.,Eklund, H. (deposition date: 2008-02-26, release date: 2008-04-29, Last modification date: 2023-12-13)

Primary citation

Mikkelsen, N.E.,Munch-Petersen, B.,Eklund, H.
Structural Studies of Nucleoside Analog and Feedback Inhibitor Binding to Drosophila Melanogaster Multisubstrate Deoxyribonucleoside Kinase.
FEBS J., 275:2151-, 2008

PubMed Abstract: The Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (dNK; EC 2.7.1.145) has a high turnover rate and a wide substrate range that makes it a very good candidate for gene therapy. This concept is based on introducing a suicide gene into malignant cells in order to activate a prodrug that eventually may kill the cell. To be able to optimize the function of dNK, it is vital to have structural information of dNK complexes. In this study we present crystal structures of dNK complexed with four different nucleoside analogs (floxuridine, brivudine, zidovudine and zalcitabine) and relate them to the binding of substrate and feedback inhibitors. dCTP and dGTP bind with the base in the substrate site, similarly to the binding of the feedback inhibitor dTTP. All nucleoside analogs investigated bound in a manner similar to that of the pyrimidine substrates, with many interactions in common. In contrast, the base of dGTP adopted a syn-conformation to adapt to the available space of the active site.

PubMed: 18384378
DOI: 10.1111/J.1742-4658.2008.06369.X

Experimental method

X-RAY DIFFRACTION (2.2 Å)