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Thymidine kinase

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{{STRUCTURE_1e2j| PDB=1e2j | SIZE=400| SCENE= |right| CAPTION=Human thymidine kinase dimer complex with thymidine and sulfate, [[1e2j]] }}
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<StructureSection load='2j9r' size='350' side='right' caption='Thymidine kinase complex with thymidine, phosphate and Zn+2 ion (grey) (PDB entry [[2j94]])' scene='45/455455/Cv/1'>
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== Function ==
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'''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''' <ref>PMID:18459168</ref>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]].
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'''Thymidine kinase''' (TK) catalyzes the conversion of deoxythymidine (THM) to deoxythymidine 5’-phosphate (THMP) with the coversion 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 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.
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== Relevance ==
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TK1 level in serum is a marker for leukemia and lymphoma<ref>PMID:16142366</ref>.
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{{TOC limit|limit=2}}
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== Disease ==
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Mutations in TK2 are associated with mitochondrial DNA depletion<ref>PMID:11687801</ref>.
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== Structural highlights ==
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The biological assembly of Thymidine kinase is <scene name='45/455455/Cv/5'>homotetramer</scene>. <scene name='45/455455/Cv/6'>Thymidine and phosphate are bound in the hydrophobic active site pocket of TK</scene><ref>PMID:17288553</ref>. Water molecules are shown as red spheres.
== 3D Structures of thymidine kinase ==
== 3D Structures of thymidine kinase ==
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[[Thymidine kinase 3D structures]]
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</StructureSection>
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''Updated December 2011''
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== References ==
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<references/>
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[[1e2h]] – HsvTK – Herpes simplex virus 1<BR />
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[[3e2i]] – TK – ''Staphylococcus aureus''<BR />
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[[2qpo]] – TmTK – ''Thermotoga maritima''
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===Thymidine kinase complex with reactants or products===
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[[1e2i]] - HsvTK + hydroxypropyladenine<BR />
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[[1e2j]] - HsvTK (mutant) + THM<BR />
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[[1kim]] - HsvTK + THM<BR />
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[[1vtk]] - HsvTK + THMP + ADP<BR />
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[[2vtk]] - HsvTK + THM + ADP<BR />
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[[3vtk]] - HsvTK + substrate analog + ADP<BR />
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[[3f0t]], [[1of1]] – HsvTK residues 45-376 + thymine derivative <BR />
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[[3rdp]] - HsvTK residues 45-376 + pyrimidine derivative<br />
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[[1qhi]], [[1ki3]], [[1ki5]], [[1ki2]], [[1ki4]] - HsvTK + inhibitor<BR />
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[[1e2p]], [[1e2m]], [[1e2n]], [[1e2k]], [[1e2l]], [[1ki6]], [[1ki7]], [[1ki8]] – HsvTK + substrate analog<BR />
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[[1osn]] – TK + inhibitor + ADP - Human Herpes virus 3<BR />
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[[1p6x]] – EhvTK + THM – Equine Herpes virus 4<BR />
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[[1p72]] - EhvTK + THM + ADP<BR />
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[[2qqe]] – TmTK + THM<BR />
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[[2qq0]]– TmTK + THM + ADP + THMP + ANP<BR />
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[[2b8t]] - TK + THM – ''Ureaplasma parvum''<BR />
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[[2j9r]] – TK + THM – ''Bacillus anthracis''<BR />
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[[1xx6]] – TK + ADP – ''Clostridium acetobutylicum''
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===Thymidine kinase complex with feed-back inhibitor===
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[[2j87]] – TK + TTP – Vaccinia virus<BR />
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[[2uz3]] – TK (mutant) + TTP – ''Ureaplasma urealyticum''<BR />
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[[2ja1]] – TK + TTP – ''Bacillus cereus''
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===Thymidine kinase complex with bisubstrate inhibitor===
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[[1p7c]] – HsvTK + TP5A<BR />
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[[1p73]] - EhvTK + TP4A<BR />
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[[1p75]] - EhvTK + TP5A<BR />
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[[2orw]] – TmTK + TP4A<BR />
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[[2ki5]] – HsvTK + aciclovir
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===Thymidine kinase 1===
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[[1xbt]] - hTK1 residues 1-193 – human<BR />
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[[2wvj]] – hTK1 residues 1-193 (mutant) + TTP<BR />
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[[2orv]] – hTK1 (mutant) + TP4A<BR />
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===Thymidine kinase 2===
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[[1w4r]] – hTK2 + TTP
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[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

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

Drag the structure with the mouse to rotate

References

  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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