Thymidine kinase

Function

Thymidine kinase or deoxyribonucleoside kinase (TK) catalyzes the conversion of deoxythymidine (THM) to deoxythymidine 5’-phosphate (THMP) with the conversion of ATP to ADP. TK has an important role in the synthesis of DNA. It is required for the action of many antiviral drugs. Higher organisms have 2 isozymes. TK1 is cell cycle-dependent while TK2 ^[1]is found in the mitochondria and is cell cycle-independent. TK undergoes feed-back regulation by thymidine triphosphate (TTP). Adenosyl-thymidyl-tetraphosphate (TP4A) is a bisubstrate inhibitor of TK. For more details see Herpes Simplex Virus Thymidine Kinase and drug Aciclovir.

Relevance

TK1 level in serum is a marker for leukemia and lymphoma^[2].

Disease

Mutations in TK2 are associated with mitochondrial DNA depletion^[3].

Structural highlights

The biological assembly of Thymidine kinase is . ^[4]. Water molecules are shown as red spheres.

3D Structures of thymidine kinase

Thymidine kinase 3D structures

Thymidine kinase complex with thymidine, phosphate and Zn+2 ion (grey) (PDB entry 2j94)

Drag the structure with the mouse to rotate

ReferencesReferences

↑ Perez-Perez MJ, Priego EM, Hernandez AI, Familiar O, Camarasa MJ, Negri A, Gago F, Balzarini J. Structure, physiological role, and specific inhibitors of human thymidine kinase 2 (TK2): present and future. Med Res Rev. 2008 Sep;28(5):797-820. doi: 10.1002/med.20124. PMID:18459168 doi:http://dx.doi.org/10.1002/med.20124
↑ He Q, Zhang P, Zou L, Li H, Wang X, Zhou S, Fornander T, Skog S. Concentration of thymidine kinase 1 in serum (S-TK1) is a more sensitive proliferation marker in human solid tumors than its activity. Oncol Rep. 2005 Oct;14(4):1013-9. PMID:16142366
↑ Saada A, Shaag A, Mandel H, Nevo Y, Eriksson S, Elpeleg O. Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. Nat Genet. 2001 Nov;29(3):342-4. PMID:11687801 doi:http://dx.doi.org/10.1038/ng751
↑ Kosinska U, Carnrot C, Sandrini MP, Clausen AR, Wang L, Piskur J, Eriksson S, Eklund H. Structural studies of thymidine kinases from Bacillus anthracis and Bacillus cereus provide insights into quaternary structure and conformational changes upon substrate binding. FEBS J. 2007 Feb;274(3):727-37. PMID:17288553 doi:10.1111/j.1742-4658.2006.05617.x

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Michal Harel, Alexander Berchansky

[1] Perez-Perez MJ, Priego EM, Hernandez AI, Familiar O, Camarasa MJ, Negri A, Gago F, Balzarini J. Structure, physiological role, and specific inhibitors of human thymidine kinase 2 (TK2): present and future. Med Res Rev. 2008 Sep;28(5):797-820. doi: 10.1002/med.20124. PMID:18459168 doi:http://dx.doi.org/10.1002/med.20124

[2] He Q, Zhang P, Zou L, Li H, Wang X, Zhou S, Fornander T, Skog S. Concentration of thymidine kinase 1 in serum (S-TK1) is a more sensitive proliferation marker in human solid tumors than its activity. Oncol Rep. 2005 Oct;14(4):1013-9. PMID:16142366

[3] Saada A, Shaag A, Mandel H, Nevo Y, Eriksson S, Elpeleg O. Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. Nat Genet. 2001 Nov;29(3):342-4. PMID:11687801 doi:http://dx.doi.org/10.1038/ng751

[4] Kosinska U, Carnrot C, Sandrini MP, Clausen AR, Wang L, Piskur J, Eriksson S, Eklund H. Structural studies of thymidine kinases from Bacillus anthracis and Bacillus cereus provide insights into quaternary structure and conformational changes upon substrate binding. FEBS J. 2007 Feb;274(3):727-37. PMID:17288553 doi:10.1111/j.1742-4658.2006.05617.x

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