| INTRODUCTION TO THYMIDINE KINASE
To the right is a spacefill model of tk from HSV-1 (Herpes Simplex
Viruw-1).
tk facts:
- HSV-1 tk is 374 residues long (376 residues per subunit), and
functions as a homodimer.
- tk is located in the cytoplasm of all human nerve cells. It is
required by HSV-1 to infect neighboring cells, and the transmition
from one human to another.
- If dTMP is not ultimately phosphorylated, the phosphorylation
cascade cannot continue, which ultimately results in HSV-1.
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why is tk useful?
- Recently, tk was used with other drugs (aciclovir and gangciclovir)
in gene therapy for colon cancer, breast cancer, and AIDS.
- Further understanding of the mechanism of HSV-1 tk could lead
to rational design of antiviral drugs and to customized drug-specific
tk for gene therapy.
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tk is a tricky enzyme
- In order to stop phosphorylation (and infection of HSV-1), tk
cannot just be knocked out of the cell. There needs to be some
activity, because the antiviral drugs need to be phosphorylized,
in order to work.
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