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Structural basis for substrate specificities of cellular deoxyribonucleoside kinases

Nature Structural Biology volume 8, pages 616–620 (2001)Cite this article

An Erratum to this article was published on 01 September 2001

Abstract

Deoxyribonucleoside kinases phosphorylate deoxyribonucleosides and activate a number of medically important nucleoside analogs. Here we report the structure of the Drosophila deoxyribonucleoside kinase with deoxycytidine bound at the nucleoside binding site and that of the human deoxyguanosine kinase with ATP at the nucleoside substrate binding site. Compared to the human kinase, the Drosophila kinase has a wider substrate cleft, which may be responsible for the broad substrate specificity of this enzyme. The human deoxyguanosine kinase is highly specific for purine substrates; this is apparently due to the presence of Arg 118, which provides favorable hydrogen bonding interactions with the substrate. The two new structures provide an explanation for the substrate specificity of cellular deoxyribonucleoside kinases.

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Figure 1: Structures of dNK and dGK.
Figure 2: Initial electron density maps of dNK and dGK.
Figure 3: Nucleoside/nucleotide binding to dNK and dGK.

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Acknowledgements

We would like to thank A.-E. Egholm for excellent technical assistance. This work was supported by grants from the Swedish Natural Science Research Council, the Swedish Strategic Research Foundation (to H.E and S.E.), the Swedish Cancer Foundation (to H.E.), the Danish Research Council (to J.P.) and the Swedish Medical Research Council (to S.E.).

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Authors and Affiliations

  1. Department of Molecular Biology, Swedish University of Agricultural Sciences, Box 590, Biomedical Center, Uppsala, S-751 24, Sweden

    Kenth Johansson, S. Ramaswamy & Hans Eklund

  2. Department of Biochemistry, Bowen Science Building, University of Iowa, Iowa City, 52242-1109, Iowa, USA

    S. Ramaswamy

  3. Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences, Box 575, Biomedical Center, Uppsala, S-751 24, Sweden

    Catarina Ljungcrantz & Staffan Eriksson

  4. Department of Microbiology, Technical University of Denmark, Lyngby, DK-2800, Denmark

    Wolfgang Knecht & Jure Piškur

  5. Department of Life Sciences and Chemistry, Roskilde University, Roskilde, DK-4000, Denmark

    Birgitte Munch-Petersen

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Correspondence to Hans Eklund.

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Johansson, K., Ramaswamy, S., Ljungcrantz, C. et al. Structural basis for substrate specificities of cellular deoxyribonucleoside kinases. Nat Struct Mol Biol 8, 616–620 (2001). https://doi.org/10.1038/89661

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