Pasteurella multocida thymidine kinase 1 efficiently activates pyrimidine nucleoside analogs.
In the Pasteurella multocida genome only one putative deoxyribonucleoside kinase encoding gene, for thymidine kinase 1 (PmTK1), was identified. The PmTK1 gene was sub-cloned into Escherichia coli KY895 and it sensitized the host towards 2',2'-difluoro-deoxycytidine (gemcitabine, dFdC), 3'-azido-thymidine (AZT) and 5-fluoro-deoxyuridine (5F-dU). PmTK1 was over-expressed and purified with two different tags. Apparently, deoxyuridine (dU), and not thymidine (dT), is the preferred substrate. We suggest that PmTK1s could be employed as a species-specific activator of uracil-based nucleoside antibiotics.
Clausen
A R
AR
Department of Cell and Organism Biology, Lund University, Solvegatan, Lund, Sweden. Anders.Clausen@cob.lu.se
Al Meani
S A L
SA
Piskur
J
J
D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D003857:Deoxyuridine / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D016979:Pasteurella multocida / Q000201:enzymology*; D011741:Pyrimidine Nucleosides / Q000378:metabolism* / Q000494:pharmacology; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*; D015215:Zidovudine / Q000494:pharmacology; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D011741:Pyrimidine Nucleosides; D003841:Deoxycytidine; D015215:Zidovudine; D013937:Thymidine Kinase; C092717:thymidine kinase 1; D003857:Deoxyuridine; D000093542:Gemcitabine