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| [[Image:1e99.png|left|200px|thumb|Crystal structure of human thymidylate kinase complex with HIV prodrug AZTP and ADP [[1e99]]]]
| | <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)'> |
| {{STRUCTURE_1e99| PDB=1e99 | SIZE=350| SCENE= |right|CAPTION=Human thymidylate kinase complex with HIV prodrug AZTP and ADP [[1e99]] }}
| | __TOC__ |
| | == 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]]. |
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| | == Relevance == |
| | The TMK inhibitor azido-dTMP (AZTP) is an HIV AZT prodrug metabolite<ref>PMID:15722537</ref>. Inhibitors of TMK are used as antibacterial agents<ref>PMID:23043329</ref>. |
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| | | == Structural highlights == |
| | | The active site of TMK contains HIV prodrug azido-thymidine, ADP and Mg+2 ion<ref>PMID:11071809</ref>. |
| | | *<scene name='54/542330/Cv/6'>Azido-thymidine binding site</scene>. Water molecules are shown as red spheres. |
| | | *<scene name='54/542330/Cv/7'>Mg coordination site</scene>. |
| | | *<scene name='54/542330/Cv/8'>ATM binding site</scene>. |
| | | *<scene name='54/542330/Cv/9'>Whole binding site</scene>. |
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| '''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. 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. The TMK inhibitor azido-dTMP (AZTP) is an HIV AZT prodrug metabolite.
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| == 3D Structures of thymidylate kinase == | | == 3D Structures of thymidylate kinase == |
| | [[Thymidylate kinase 3D structures]] |
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| Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
| | </StructureSection> |
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| [[2cck]], [[4f4i]] – SaTMK – ''Staphylococcus aureus'' <br />
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| [[2pbr]] – TMK – ''Aquifex aeolicus'' <br />
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| [[2plr]] – TMK – ''Sulfolobus tokodaii'' <br />
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| [[3ld9]] – TMK – ''Ehrlichia chafeensis''<br />
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| [[3v9p]] – TMK – ''Burkholderia thailandensis''<br />
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| [[3uwk]], [[3uwo]] – PaTMK – ''Pseudomonas aeruginosa''<br />
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| ===TMK complex with HIV prodrug AZT derivative===
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| [[2tmk]] – yTMK + AZTP <br />
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| [[4eaq]] – SaTMK + AZTP <br />
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| [[4gmd]] – PaTMK + AZTP <br />
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| [[4tmk]], [[5tmp]] – TMK + AZTP – ''Escherichia coli''<br />
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| [[1w2h]] – MtTMK + AZTP - ''Mycobacterium tuberculosis'' <br />
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| [[1e98]], [[1e99]], [[1e9d]] – hTMK (mutant) + AZTP + ADP<br />
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| ===TMK complex with nucleotides===
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| [[2v54]] – VvTMK + TDP – Vaccinia virus<br />
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| [[2w0s]] – VvTMK + brivudin-MP <br />
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| [[1tmk]] – yTMK + dTMP - yeast<br />
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| [[4e5u]] – PaTMK + dTMP <br />
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| [[2ccg]], [[2ccj]], [[4dwj]] – SaTMK + dTMP <br />
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| [[1g3u]], [[1gsi]], [[1n5i]], [[1n5k]] – MtTMK + dTMP <br />
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| [[1w2g]] – MtTMK + thymidine <br />
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| [[1gtv]] – MtTMK + TDP <br />
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| [[1n5j]] – MtTMK + TDP + TTP<br />
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| [[1n5l]] – MtTMK + TDP + dTMP <br />
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| [[1mrs]] – MtTMK + UMP derivative <br />
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| [[3uxm]], [[4esh]] – PaTMK + deoxy thymidine derivative <br />
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| [[3hjn]] – TMK + ADP + TDP – ''Thermotoga maritima''<br />
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| [[1e2d]], [[1e2e]], [[1e2f]], [[1e9e]], [[1e9f]] – hTMK (mutant) + ADP + dTMP - human<br />
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| [[1e9f]] – hTMK (mutant) + ADP + dTMP - human<br />
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| [[4edh]] – PaTMK + ADP + dTMP <br />
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| [[3lv8]] – VcTMK + ADP + dTMP + TDP – ''Vibrio cholerae''<br />
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| [[3n2i]] – VcTMK + thymidine + thymidine deoxy-thymidine<br />
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| [[1e9b]] – hTMK (mutant) + azido-TMP + APPNP<br />
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| [[1e9c]] – hTMK (mutant) + dTMP + APPNP<br />
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| [[1nmx]] – hTMK (mutant) + F-TMP + ADP<br />
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| [[1nmy]], [[1nn0]], [[1nnz]], [[1nn1]], [[1nn3]], [[1nn5]], [[1nmz]] – hTMK (mutant) + dTMP derivative + APPNP<br />
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| [[2xx3]] – hTMK + dTMP derivative + ADP<br />
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| ===Other TMK binary complexes===
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| [[4gfd]], [[4hlc]], [[4hld]], [[4hej]], [[4hdc]] – SaTMK + antibacterial drug <br />
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| [[4gsy]] – SaTMK + inhibitor<br />
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| ===TMK complex with bisubstrate inhibitor===
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| [[1mrn]] – MtTMK + TP5A <br />
| | == References == |
| [[3tmk]] – yTMK + TP5A <br />
| | <references/> |
| [[1e9a]] – hTMK (mutant) + azido-TP5A + ADP<br /> | | [[Category:Topic Page]] |