Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T98397 | Target Info | |||
| Target Name | Thymidylate synthase (TYMS) | ||||
| Synonyms | TSase; TS | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | TYMS | ||||
| Biochemical Class | Methyltransferase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | 5-Fluoro-2'-Deoxyuridine-5'-Monophosphate | Ligand Info | |||
| Canonical SMILES | C1C(C(OC1N2C=C(C(=O)NC2=O)F)COP(=O)(O)O)O | ||||
| InChI | 1S/C9H12FN2O8P/c10-4-2-12(9(15)11-8(4)14)7-1-5(13)6(20-7)3-19-21(16,17)18/h2,5-7,13H,1,3H2,(H,11,14,15)(H2,16,17,18)/t5-,6+,7+/m0/s1 | ||||
| InChIKey | HFEKDTCAMMOLQP-RRKCRQDMSA-N | ||||
| PubChem Compound ID | 8642 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3H9K Structures of Thymidylate Synthase R163K with Substrates and Inhibitors Show Subunit Asymmetry | ||||||
| Method | X-ray diffraction | Resolution | 2.65 Å | Mutation | Yes | [1] |
| PDB Sequence |
PPHGELQYLG
35 QIQHILRCGV45 RKDDRTGTGT55 LSVFGMQARY65 SLRDEFPLLT75 TKRVFWKGVL 85 EELLWFIKGS95 TNAKELSSKG105 VKIWDANGSR115 DFLDSLGFST125 REEGDLGPVY 135 GFQWRHFGAE145 YRDMESDYSG155 QGVDQLQKVI165 DTIKTNPDDR175 RIIMCAWNPR 185 DLPLMALPPC195 HALCQFYVVN205 SELSCQLYQR215 SGDMGLGVPF225 NIASYALLTY 235 MIAHITGLKP245 GDFIHTLGDA255 HIYLNHIEPL265 KIQLQREPRP275 FPKLRILRKV 285 EKIDDFKAED295 FQIEGYNPHP305 T
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| PDB ID: 6QXG Crystal structure of His-tag human thymidylate synthase (HT-hTS) in complex with FdUMP | ||||||
| Method | X-ray diffraction | Resolution | 2.08 Å | Mutation | No | [2] |
| PDB Sequence |
PPHGELQYLG
35 QIQHILRCGV45 RKDDRTGTGT55 LSVFGMQARY65 SLRDEFPLLT75 TKRVFWKGVL 85 EELLWFIKGS95 TNAKELSSKG105 VKIWDANGSR115 DFLDSLGFST125 REEGDLGPVY 135 GFQWRHFGAE145 YRDMESDYSG155 QGVDQLQRVI165 DTIKTNPDDR175 RIIMCAWNPR 185 DLPLMALPPC195 HALCQFYVVN205 SELSCQLYQR215 SGDMGLGVPF225 NIASYALLTY 235 MIAHITGLKP245 GDFIHTLGDA255 HIYLNHIEPL265 KIQLQREPRP275 FPKLRILRKV 285 EKIDDFKAED295 FQIEGYNPHP305 TIKMEMA
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| PDB ID: 6ZXO Crystal structure of His-tagged human thymidylate synthase (HT-hTS) in complex with FdUMP and Raltitrexed (Tomudex) | ||||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [3] |
| PDB Sequence |
> Chain A
PPHGELQYLG 35 QIQHILRCGV45 RKDDRTGTGT55 LSVFGMQARY65 SLRDEFPLLT75 TKRVFWKGVL 85 EELLWFIKGS95 TNAKELSSKG105 VKIWDANGSR115 DFLDSLGFST125 REEGDLGPVY 135 GFQWRHFGAE145 YRDMESDYSG155 QGVDQLQRVI165 DTIKTNPDDR175 RIIMCAWNPR 185 DLPLMALPPC195 HALCQFYVVN205 SELSCQLYQR215 SGDMGLGVPF225 NIASYALLTY 235 MIAHITGLKP245 GDFIHTLGDA255 HIYLNHIEPL265 KIQLQREPRP275 FPKLRILRKV 285 EKIDDFKAED295 FQIEGYNPHP305 TIKMEMAV> Chain F PPHGELQYLG 35 QIQHILRCGV45 RKDDRTGTGT55 LSVFGMQARY65 SLRDEFPLLT75 TKRVFWKGVL 85 EELLWFIKGS95 TNAKELSSKG105 VKIWDANGSR115 DFLDSLGFST125 REEGDLGPVY 135 GFQWRHFGAE145 YRDMESDYSG155 QGVDQLQRVI165 DTIKTNPDDR175 RIIMCAWNPR 185 DLPLMALPPC195 HALQFYVVNS206 ELSCQLYQRS216 GDMGLGVPFN226 IASYALLTYM 236 IAHITGLKPG246 DFIHTLGDAH256 IYLNHIEPLK266 IQLQREPRPF276 PKLRILRKVE 286 KIDDFKAEDF296 QIEGYNPHPT306 IKMEMA
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ARG50[A]
2.841
TRP109[A]
3.444
TYR135[A]
4.560
LEU192[A]
4.125
PRO193[A]
4.618
CYS195[A]
3.341
HIS196[A]
3.502
GLN214[A]
3.372
ARG215[A]
2.852
SER216[A]
2.726
GLY217[A]
3.655
ASP218[A]
2.819
GLY222[A]
3.786
VAL223[A]
4.490
ASN226[A]
2.720
HIS256[A]
2.903
TYR258[A]
2.929
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structures of human thymidylate synthase R163K with dUMP, FdUMP and glutathione show asymmetric ligand binding. Acta Crystallogr D Biol Crystallogr. 2011 Jan;67(Pt 1):60-6. | ||||
| REF 2 | Structural Comparison of Enterococcus faecalis and Human Thymidylate Synthase Complexes with the Substrate dUMP and Its Analogue FdUMP Provides Hints about Enzyme Conformational Variabilities. Molecules. 2019 Mar 31;24(7):1257. | ||||
| REF 3 | Structural Bases for the Synergistic Inhibition of Human Thymidylate Synthase and Ovarian Cancer Cell Growth by Drug Combinations. Cancers (Basel). 2021 Apr 24;13(9):2061. | ||||
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