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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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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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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DOI: https://doi.org/10.1038/89661
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