Investigation of the substrate recognition of Drosophila melanogaster nucleoside kinase by site directed mutagenesis.
The deoxyribonucleoside kinase of Drosophila melanogaster (Dm-dNK) has a broad substrate specificity and a higher catalytic rate than other known deoxyribonucleoside kinases. Therefore it is a natural candidate for possible use as a suicide gene in combined gene/chemotherapy of cancer. We have performed site directed mutagenesis and tested different truncated forms of the enzyme in order to increase the affinity for ganciclovir.
Solaroli
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N
Division of Clinical Virology F68, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Bjerke
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M
Johansson
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M
Karlsson
A
A
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001665:Binding Sites; D002384:Catalysis; D002855:Chromatography, Thin Layer; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster / Q000201:enzymology*; D015774:Ganciclovir / Q000494:pharmacology; D015316:Genetic Therapy / Q000379:methods*; D005982:Glutathione Transferase / Q000378:metabolism; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000628:therapy*; D009705:Nucleosides / Q000737:chemistry; D010770:Phosphotransferases / Q000737:chemistry*; D013379:Substrate Specificity
D000998:Antiviral Agents; D009705:Nucleosides; D005982:Glutathione Transferase; D010770:Phosphotransferases; C021892:nucleoside phosphotransferase; D015774:Ganciclovir