Thymidylate kinase

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<StructureSection load='' size='350' side='right' scene='54/542330/Cv/1' caption='Human thymidylate kinase complex with HIV prodrug AZTP, ADP and Mg+2 ion (green)'>
<StructureSection load='' size='350' side='right' scene='54/542330/Cv/1' caption='Human thymidylate kinase complex with HIV prodrug AZTP, ADP and Mg+2 ion (green)'>
-
 
+
__TOC__
== Function ==
== Function ==
'''Thymidylate kinase''' (TMK) catalyzes the conversion of thymidine-5’-phosphate (dTMP) and ATP to thymidine-5’-diphosphate and ADP. TMK is important for DNA synthesis<ref>PMID:23394555</ref>. Inhibitors of TMK include bisubstrate compounds of the type TP(n)X where P(n) are the number of phosphoryl groups and X is the nucleoside moiety of the acceptor. For more details see [[Student Project 8 for UMass Chemistry 423 Spring 2015]].
'''Thymidylate kinase''' (TMK) catalyzes the conversion of thymidine-5’-phosphate (dTMP) and ATP to thymidine-5’-diphosphate and ADP. TMK is important for DNA synthesis<ref>PMID:23394555</ref>. Inhibitors of TMK include bisubstrate compounds of the type TP(n)X where P(n) are the number of phosphoryl groups and X is the nucleoside moiety of the acceptor. For more details see [[Student Project 8 for UMass Chemistry 423 Spring 2015]].
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*<scene name='54/542330/Cv/8'>ATM binding site</scene>.
*<scene name='54/542330/Cv/8'>ATM binding site</scene>.
*<scene name='54/542330/Cv/9'>Whole binding site</scene>.
*<scene name='54/542330/Cv/9'>Whole binding site</scene>.
 +
== 3D Structures of thymidylate kinase ==
 +
[[Thymidylate kinase 3D structures]]
 +
</StructureSection>
</StructureSection>
== 3D Structures of thymidylate kinase ==
== 3D Structures of thymidylate kinase ==
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**[[3v9p]] – TMK – ''Burkholderia thailandensis''<br />
**[[3v9p]] – TMK – ''Burkholderia thailandensis''<br />
**[[3uwk]], [[3uwo]] – PaTMK – ''Pseudomonas aeruginosa''<br />
**[[3uwk]], [[3uwo]] – PaTMK – ''Pseudomonas aeruginosa''<br />
 +
**[[5x7j]], [[5xak]], [[5xt8]] – TtTMK – ''Thermus thermophilus''<br />
 +
**[[5x8d]], [[5x8j]], [[5x8k]], [[5x8v]], [[5x98]], [[5x99]], [[5xal]] – TtTMK (mutant)<br />
*Thymidylate kinase complex with HIV prodrug AZT derivative
*Thymidylate kinase complex with HIV prodrug AZT derivative
 +
**[[1e98]], [[1e99]], [[1e9d]] – hTMK (mutant) + AZTP + ADP - human<br />
**[[2tmk]] – yTMK + AZTP <br />
**[[2tmk]] – yTMK + AZTP <br />
**[[4eaq]] – SaTMK + AZTP <br />
**[[4eaq]] – SaTMK + AZTP <br />
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**[[4tmk]], [[5tmp]] – TMK + AZTP – ''Escherichia coli''<br />
**[[4tmk]], [[5tmp]] – TMK + AZTP – ''Escherichia coli''<br />
**[[1w2h]] – MtTMK + AZTP - ''Mycobacterium tuberculosis'' <br />
**[[1w2h]] – MtTMK + AZTP - ''Mycobacterium tuberculosis'' <br />
-
**[[1e98]], [[1e99]], [[1e9d]] – hTMK (mutant) + AZTP + ADP<br />
 
-
*Thymidylate kinase complex with nucleotides
+
*Thymidylate kinase complex with one nucleotide
 +
**[[1tmk]] – yTMK + dTMP - yeast<br />
**[[2v54]] – VvTMK + TDP – Vaccinia virus<br />
**[[2v54]] – VvTMK + TDP – Vaccinia virus<br />
**[[2w0s]] – VvTMK + brivudin-MP <br />
**[[2w0s]] – VvTMK + brivudin-MP <br />
-
**[[1tmk]] – yTMK + dTMP - yeast<br />
 
**[[4e5u]] – PaTMK + dTMP <br />
**[[4e5u]] – PaTMK + dTMP <br />
 +
**[[3uxm]], [[4esh]] – PaTMK + deoxy thymidine derivative <br />
**[[2ccg]], [[2ccj]], [[4dwj]] – SaTMK + dTMP <br />
**[[2ccg]], [[2ccj]], [[4dwj]] – SaTMK + dTMP <br />
**[[1g3u]], [[1gsi]], [[1n5i]], [[1n5k]] – MtTMK + dTMP <br />
**[[1g3u]], [[1gsi]], [[1n5i]], [[1n5k]] – MtTMK + dTMP <br />
**[[1w2g]] – MtTMK + thymidine <br />
**[[1w2g]] – MtTMK + thymidine <br />
**[[1gtv]] – MtTMK + TDP <br />
**[[1gtv]] – MtTMK + TDP <br />
-
**[[1n5j]] – MtTMK + TDP + TTP<br />
 
-
**[[1n5l]] – MtTMK + TDP + dTMP <br />
 
**[[1mrs]] – MtTMK + UMP derivative <br />
**[[1mrs]] – MtTMK + UMP derivative <br />
-
**[[3uxm]], [[4esh]] – PaTMK + deoxy thymidine derivative <br />
+
**[[2yof]], [[2yog]], [[2yoh]] - TMK + thymidine analog – ''Plasmodium falciparum''<br />
-
**[[3hjn]] – TMK + ADP + TDP – ''Thermotoga maritima''<br />
+
**[[5xai]] – AaTMK + TMP <br />
-
**[[1e2d]], [[1e2e]], [[1e2f]], [[1e9e]], [[1e9f]] – hTMK (mutant) + ADP + dTMP - human<br />
+
**[[5x86]] – TtTMK + dTMP <br />
-
**[[1e9f]] – hTMK (mutant) + ADP + dTMP - human<br />
+
**[[5x8a]] – TtTMK + ATP <br />
-
**[[4edh]] – PaTMK + ADP + dTMP <br />
+
 
-
**[[3lv8]] – VcTMK + ADP + dTMP + TDP – ''Vibrio cholerae''<br />
+
*Thymidylate kinase complex with two nucleotides
-
**[[3n2i]] – VcTMK + thymidine + thymidine deoxy-thymidine<br />
+
 
 +
**[[1e2d]], [[1e2e]], [[1e2f]], [[1e9e]], [[1e9f]] – hTMK (mutant) + ADP + dTMP<br />
 +
**[[1e2q]] – hTMK (mutant) + ATP + dTMP<br />
 +
**[[1e9f]] – hTMK (mutant) + ADP + dTMP<br />
**[[1e9b]] – hTMK (mutant) + azido-TMP + APPNP<br />
**[[1e9b]] – hTMK (mutant) + azido-TMP + APPNP<br />
**[[1e9c]] – hTMK (mutant) + dTMP + APPNP<br />
**[[1e9c]] – hTMK (mutant) + dTMP + APPNP<br />
**[[1nmx]] – hTMK (mutant) + F-TMP + ADP<br />
**[[1nmx]] – hTMK (mutant) + F-TMP + ADP<br />
**[[1nmy]], [[1nn0]], [[1nnz]], [[1nn1]], [[1nn3]], [[1nn5]], [[1nmz]] – hTMK (mutant) + dTMP derivative + APPNP<br />
**[[1nmy]], [[1nn0]], [[1nnz]], [[1nn1]], [[1nn3]], [[1nn5]], [[1nmz]] – hTMK (mutant) + dTMP derivative + APPNP<br />
-
**[[2xx3]] – hTMK + dTMP derivative + ADP<br />
+
**[[2xx3]] – hTMK + dTMP derivative + ADP<br />>
-
**[[2yof]], [[2yog]], [[2yoh]] - TMK + thymidine analog – ''Plasmodium falciparum''<br />
+
**[[4edh]] – PaTMK + ADP + dTMP <br />
 +
**[[1n5j]] – MtTMK + TDP + TTP<br />
 +
**[[1n5l]] – MtTMK + TDP + dTMP <br />
 +
**[[3hjn]] – TMK + ADP + TDP – ''Thermotoga maritima''<br />
 +
**[[3lv8]] – VcTMK + ADP + dTMP + TDP – ''Vibrio cholerae''<br />
 +
**[[3n2i]] – VcTMK + thymidine + thymidine deoxy-thymidine<br />
**[[4s35]] – AaTMK + dTMP + AMPPCP<br />
**[[4s35]] – AaTMK + dTMP + AMPPCP<br />
**[[5h56]] – AaTMK + dTDP + ADP<br />
**[[5h56]] – AaTMK + dTDP + ADP<br />
**[[5xb2]], [[5xb3]] – AaTMK + dTMP + ADP<br />
**[[5xb2]], [[5xb3]] – AaTMK + dTMP + ADP<br />
**[[5h5k]] – AaTMK + CMP + ATP<br />
**[[5h5k]] – AaTMK + CMP + ATP<br />
-
**[[5xai]] – AaTMK + TMP <br />
 
**[[5uiv]] - TMK + TMP + ADP – ''Candida albicans''<br />
**[[5uiv]] - TMK + TMP + ADP – ''Candida albicans''<br />
 +
**[[5x8b]] – TtTMK + TMP + ADP + ATP <br />
 +
**[[5zax]] – TtTMK + TMP + ADP + TDP <br />
 +
**[[5zb0]] – TtTMK + ADP + TDP <br />
 +
**[[5zb4]] – TtTMK + ADP + TMP <br />
 +
**[[5x8c]] – TtTMK + dTMP + AMPPCP<br />
*Other thymidylate kinase binary complexes
*Other thymidylate kinase binary complexes
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**[[4gfd]], [[4hlc]], [[4hld]], [[4hej]], [[4hdc]] – SaTMK + antibacterial drug <br />
**[[4gfd]], [[4hlc]], [[4hld]], [[4hej]], [[4hdc]] – SaTMK + antibacterial drug <br />
**[[4gsy]], [[4qg7]], [[4xwa]] – SaTMK + inhibitor<br />
**[[4gsy]], [[4qg7]], [[4xwa]] – SaTMK + inhibitor<br />
-
**[[4qg7]], [[4qgf]], [[4qgg]], [[4qgh]] – SaTMK (mutant) + inhibitor<br />
+
**[[4qg7]], [[4qgf]], [[4qgg]], [[4qgh]], [[4qga]] – SaTMK (mutant) + inhibitor<br />
**[[4mqb]] – SaTMK + MES<br />
**[[4mqb]] – SaTMK + MES<br />
**[[4unp]], [[4unq]], [[4unn]], [[4unr]], [[4uns]] – MtTMK + inhibitor<br />
**[[4unp]], [[4unq]], [[4unn]], [[4unr]], [[4uns]] – MtTMK + inhibitor<br />

Revision as of 11:12, 23 February 2020

Human thymidylate kinase complex with HIV prodrug AZTP, ADP and Mg+2 ion (green)

Drag the structure with the mouse to rotate

3D Structures of thymidylate kinase

Updated on 23-February-2020

References

  1. ↑ Cui Q, Shin WS, Luo Y, Tian J, Cui H, Yin D. Thymidylate kinase: an old topic brings new perspectives. Curr Med Chem. 2013;20(10):1286-305. PMID:23394555
  2. ↑ Wohrl BM, Loubiere L, Brundiers R, Goody RS, Klatzmann D, Konrad M. Expressing engineered thymidylate kinase variants in human cells to improve AZT phosphorylation and human immunodeficiency virus inhibition. J Gen Virol. 2005 Mar;86(Pt 3):757-64. PMID:15722537 doi:http://dx.doi.org/10.1099/vir.0.80529-0
  3. ↑ Martinez-Botella G, Breen JN, Duffy JE, Dumas J, Geng B, Gowers IK, Green OM, Guler S, Hentemann MF, Hernandez-Juan FA, Joseph-McCarthy D, Kawatkar SP, Larsen NA, Lazari O, Loch JT, Macritchie JA, McKenzie AR, Newman JV, Olivier NB, Otterson LG, Owens AP, Read J, Sheppard DW, Keating TA. Discovery of Selective and Potent Inhibitors of Gram-positive Bacterial Thymidylate Kinase (TMK). J Med Chem. 2012 Oct 8. PMID:23043329 doi:http://dx.doi.org/10.1021/jm3011806
  4. ↑ Ostermann N, Lavie A, Padiyar S, Brundiers R, Veit T, Reinstein J, Goody RS, Konrad M, Schlichting I. Potentiating AZT activation: structures of wild-type and mutant human thymidylate kinase suggest reasons for the mutants' improved kinetics with the HIV prodrug metabolite AZTMP. J Mol Biol. 2000 Nov 17;304(1):43-53. PMID:11071809 doi:10.1006/jmbi.2000.4175

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