Effect of C-Terminal of Human Cytosolic Thymidine Kinase (TK1) on in Vitro Stability and Enzymatic Properties

  title={Effect of C-Terminal of Human Cytosolic Thymidine Kinase (TK1) on in Vitro Stability and Enzymatic Properties},
  author={C. Zhu and L. S. Harlow and Dvora Berenstein and Sten Munch-Petersen and Birgitte Munch‐Petersen},
  journal={Nucleosides, Nucleotides \& Nucleic Acids},
  pages={1185 - 1188}
Thymidine kinase (TK1) is a key enzyme in the salvage pathway of nucleotide metabolism and catalyzes the first rate-limiting step in the synthesis of dTTP, transfer of a gamma-phosphate group from a nucleoside triphosphate to the 5′-hydroxyl group of thymidine, thus forming dTMP. TK1 is cytosolic and its activity fluctuates during cell cycle coinciding with the DNA synthesis rate and disappears during mitosis. This fluctuation is important for providing a balanced supply of dTTP for DNA… 

Molecular properties of serum thymidine kinase 1 and use of the canine enzyme in disease monitoring

Investigating the molecular characteristics of canine thymidine kinase 1 and utilizing several anti-TK1 antibodies to a better understanding its role in disease prognostics, risk assessment, and monitoring of cancer development revealed that serum TK1 activity was elevated in 41% of bitches with pyometra, and thus TK 1 determinations may be clinically valuable also in some non-neoplastic diseases.

Thymidine Kinases from Human and Caenorhabditis elegans and their Active Site Mutants

The enzyme is compared with HuTK1 with regard to substrate specificity, native size, activation by ATP, stability and kinetic parameters for dThd, and CeTk1 is truncated in the C-terminal to see how the truncation affects stability and activity.

Feline thymidine kinase 1: molecular characterization and evaluation of its serum form as a diagnostic biomarker

The results suggest that serum TK1 may be a promising biomarker for the diagnosis and monitoring of malignant diseases and for the differential diagnosis of certain inflammatory disease.

Comparative active‐site mutation study of human and Caenorhabditis elegans thymidine kinase 1

A detailed, mutation‐based comparative structure–function study of the active sites of two thymidine kinases shows that this TK1 mutant could be suitable for suicide gene therapy.

Deoxynucleotide biosynthesis and regulation : a study of deoxynucleoside kinases and deoxynucleotide pools

Higher thymidine levels in the TKcells caused by defectThymidine salvage to dTTP protects against UV irradiation, and these results suggest that balanced deoxynucleotide pools are important for correct DNA repair.

Purification and Characterization of Wild-Type and Mutant Tk1 Type Kinases From Caenorhabditis Elegans

Caenorhabditis elegans has a single deoxynucleoside kinase-like gene, but besides accepting thymidine as a substrate, the C. elegans TK1 also phosphorylates deoxyguanosine.

Thymidine kinase 1 through the ages: a comprehensive review

Compared to other proliferation markers, TK1 levels during S phase more accurately determine the rate of DNA synthesis in actively dividing tumors, and is potentially more advantageous than current biomarkers.

Comparative Study of Thymidine Kinase -1 and Total Antioxidant Capacity in Iraqi Children with Platelet Count Disorder

It is concluded that TK-1 may be a novel biomarker for platelet count disorder disease and there was a probability of expose children patients with thrombocytopenia and with thROMbocytosis for tumor diseases.

Detection of Thymidine Kinase 1 Activity in Whole Blood Using an Oligonucleotide System

In today’s medical science studies, many tumor markers are being used to monitor cancer cell proliferation, but the number of assays for analysis of these markers are few. The aim of this study was

Intracellular immunity: finding the enemy within—how cells recognize and respond to intracellular pathogens

In this review, this work examines the strategies that cells use to detect and destroy pathogens once the cell membrane has been penetrated.



Cell cycle regulation of thymidine kinase: residues near the carboxyl terminus are essential for the specific degradation of the enzyme at mitosis.

It is demonstrated that residues near the carboxyl terminus of TK are essential for the cell cycle phase-specific degradation of the enzyme.

Effect of valine 106 on structure-function relation of cytosolic human thymidine kinase. Kinetic properties and oligomerization pattern of nine substitution mutants of V106.

It is concluded that size and conformation of amino acid 106 are more important than polarity for the catalytic activity and oligomerization of TK1.

Structures of thymidine kinase 1 of human and mycoplasmic origin

  • M. WelinU. Kosińska H. Eklund
  • Chemistry, Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2004
The TK1 structure differs fundamentally from the structures of the other deoxyribonucleoside kinases, indicating a different evolutionary origin.

Mitotic Degradation of Human Thymidine Kinase 1 Is Dependent on the Anaphase-Promoting Complex/Cyclosome-Cdh1-Mediated Pathway

It is concluded that activation of the APC/C-Cdh1 complex during mitotic exit controls timing of hTK1 destruction, thus effectively minimizing dTTP formation from the salvage pathway in the early G1 phase of the cell cycle in mammalian cells.

Valine, Not Methionine, Is Amino Acid 106 in Human Cytosolic Thymidine Kinase (TK1)

Because valine with high probability is the naturally occurring amino acid at position 106 in human TK1 and because this position has high impact on the enzyme properties, the Val-106 form should be used in future investigations of recombinant human Tk1.

Reversible ATP-dependent transition between two forms of human cytosolic thymidine kinase with different enzymatic properties.