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Structure-function studies of human cytosolic thymidine kinase
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Nucleoside prodrugs, such as acyclovir, have been used for decades against cancer and viral infections. These prodrugs must be phosphorylated in order to interfere with DNA synthesis. The first phosphorylation step is carried out by deoxynucleoside kinases, dNKs. In order to develop drugs which only affect cancerous cells or viral and bacterial enzymes, but not the healthy cells of the body, it is necessary to characterize the responsible phosphorylating enzymes. This book gives an all-round literature overview of a human dNK - TK1, with a short summary of the latest publications provided in the epilogue. The experimental part concentrates on two different regions of TK1, the amino acid 106 and the C-terminal segment, and their importance for the structure and function of the enzyme. Regulation of TK1 activity by the concentration of TK1 protein, presence of ATP and the phosphorylation status of the enzyme is discussed. This book is aimed at students and scientists in the field of biochemistry, molecular biology and pharmacy interested in anticancer and antiviral/antibacterial nucleoside analogues and their activating enzymes, as well as in basal aspects of enzyme regulation.
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