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 | S-Methylthiocysteine | Ligand Info | |||
| Canonical SMILES | CSSCC(C(=O)O)N | ||||
| InChI | 1S/C4H9NO2S2/c1-8-9-2-3(5)4(6)7/h3H,2,5H2,1H3,(H,6,7)/t3-/m0/s1 | ||||
| InChIKey | PYFNLWPQPNXHCS-VKHMYHEASA-N | ||||
| PubChem Compound ID | 3080775 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6QXH Crystal structure of His-tag human thymidylate synthase (HT-hTS) in complex with dUMP | ||||||
| Method | X-ray diffraction | Resolution | 2.04 Å | Mutation | No | [1] |
| PDB Sequence |
PPHGELQYLG
35 QIQHILRGVR46 KDDRTGTGTL56 SVFGMQARYS66 LRDEFPLLTT76 KRVFWKGVLE 86 ELLWFIKGST96 NAKELSSKGV106 KIWDANGSRD116 FLDSLGFSTR126 EEGDLGPVYG 136 FQWRHFGAEY146 RDMESDYSGQ156 GVDQLQRVID166 TIKTNPDDRR176 IIMCAWNPRD 186 LPLMALPPCH196 ALCQFYVVNS206 ELSCQLYQRS216 GDMGLGVPFN226 IASYALLTYM 236 IAHITGLKPG246 DFIHTLGDAH256 IYLNHIEPLK266 IQLQREPRPF276 PKLRILRKVE 286 KIDDFKAEDF296 QIEGYNPHPT306 IKMEMA
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| PDB ID: 6QYQ Crystal structure of human thymidylate synthase (hTS) variant R175C | ||||||
| Method | X-ray diffraction | Resolution | 2.25 Å | Mutation | Yes | [2] |
| PDB Sequence |
> Chain A
EPRPPHGELQ 32 YLGQIQHILR42 CGVRKDDTGT55 LSVFGMQARY65 SLRDEFPLLT75 TKRVFWKGVL 85 EELLWFIKGS95 TNAKELSSKG105 VKIWDANGSR115 DFLDSLGFST125 REEGDLGPVY 135 GFQWRHFGAE145 YRDMESDYSG155 QGVDQLQRVI165 DTIKTNPDDC175 RIIMAWNPRD 186 LPLMALPPHA197 LQFYVVNSEL208 SCQLYQRSGD218 MGLGVPFNIA228 SYALLTYMIA 238 HITGLKPGDF248 IHTLGDAHIY258 LNHIEPLKIQ268 LQREPRPFPK278 LRILRKVEKI 288 DDFKAEDFQI298 EGYNPHPTIK308 MEM> Chain B PRPPHGELQY 33 LGQIQHILRG44 VRKDDRTGTG54 TLSVFGMQAR64 YSLRDEFPLL74 TTKRVFWKGV 84 LEELLWFIKG94 STNAKELSSK104 GVKIWDANGS114 RDFLDSLGFS124 TREEGDLGPV 134 YGFQWRHFGA144 EYRDMESDYS154 GQGVDQLQRV164 IDTIKTNPDD174 CRIIMAWNPR 185 DLPLMALPPH196 ALQFYVVNSE207 LSCQLYQRSG217 DMGLGVPFNI227 ASYALLTYMI 237 AHITGLKPGD247 FIHTLGDAHI257 YLNHIEPLKI267 QLQREPRPFP277 KLRILRKVEK 287 IDDFKAEDFQ297 IEGYNPHPTI307 KMEMA> Chain D EPRPPHGELQ 32 YLGQIQHILR42 GVRKDDRTGT53 GTLSVFGMQA63 RYSLRDEFPL73 LTTKRVFWKG 83 VLEELLWFIK93 GSTNAKELSS103 KGVKIWDANG113 SRDFLDSLGF123 STREEGDLGP 133 VYGFQWRHFG143 AEYRDMESDY153 SGQGVDQLQR163 VIDTIKTNPD173 DCRIIMCAWN 183 PRDLPLMALP193 PHALQFYVVN205 SELSCQLYQR215 SGDMGLGVPF225 NIASYALLTY 235 MIAHITGLKP245 GDFIHTLGDA255 HIYLNHIEPL265 KIQLQREPRP275 FPKLRILRKV 285 EKIDDFKAED295 FQIEGYNPHP305 TIKMEMA
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GLN138[A]
4.036
TRP139[A]
4.892
PHE142[A]
3.809
GLN160[A]
2.656
ILE178[A]
4.182
MET179[A]
1.317
ALA181[A]
1.336
TRP182[A]
3.732
ALA197[A]
3.873
LEU198[A]
3.508
TRP182[A]
3.174
PRO184[A]
3.952
ALA197[A]
4.752
TRP182[B]
3.766
PRO184[B]
4.378
ALA197[B]
4.432
LEU198[B]
4.611
GLN38[B]
4.958
HIS39[B]
2.688
ILE40[B]
3.296
LEU41[B]
3.657
ARG42[B]
1.335
GLY44[B]
1.345
VAL45[B]
3.446
SER57[B]
4.841
VAL58[B]
4.262
GLN138[B]
4.011
TRP139[B]
4.575
PHE142[B]
3.708
GLN160[B]
2.800
ILE178[B]
3.852
MET179[B]
1.331
ALA181[B]
1.350
TRP182[B]
3.713
ALA197[B]
3.764
LEU198[B]
3.624
HIS39[D]
2.871
ILE40[D]
3.350
LEU41[D]
3.531
ARG42[D]
1.354
GLY44[D]
1.340
VAL45[D]
3.589
SER57[D]
4.856
VAL58[D]
4.332
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| PDB ID: 6R2E Crystal structure of the human thymidylate synthase (hTS) interface variant Q62R | ||||||
| Method | X-ray diffraction | Resolution | 2.55 Å | Mutation | Yes | [3] |
| PDB Sequence |
> Chain A
PPHGELQYLG 35 QIQHILRGVR46 KDDRTGTGTL56 SVFGMRARYS66 LRDEFPLLTT76 KRVFWKGVLE 86 ELLWFIKGST96 NAKELSSKGV106 KIWDANGSRD116 FLDSLGFSTR126 EEGDLGPVYG 136 FQWRHFGAEY146 RDMESDYSGQ156 GVDQLQRVID166 TIKTNPDDRR176 IIMCAWNPRD 186 LPLMALPPHA197 LCQFYVVNSE207 LSCQLYQRSG217 DMGLGVPFNI227 ASYALLTYMI 237 AHITGLKPGD247 FIHTLGDAHI257 YLNHIEPLKI267 QLQREPRPFP277 KLRILRKVEK 287 IDDFKAEDFQ297 IEGYNPHPTI307 KMEMAV> Chain E PPHGELQYLG 35 QIQHILRGVR46 KDDRTGTGTL56 SVFGMRARYS66 LRDEFPLLTT76 KRVFWKGVLE 86 ELLWFIKGST96 NAKELSSKGV106 KIWDANGSRD116 FLDSLGFSTR126 EEGDLGPVYG 136 FQWRHFGAEY146 RDMESDYSGQ156 GVDQLQRVID166 TIKTNPDDRR176 IIMCAWNPRD 186 LPLMALPPHA197 LCQFYVVNSE207 LSCQLYQRSG217 DMGLGVPFNI227 ASYALLTYMI 237 AHITGLKPGD247 FIHTLGDAHI257 YLNHIEPLKI267 QLQREPRPFP277 KLRILRKVEK 287 IDDFKAEDFQ297 IEGYNPHPTI307 KMEMAV
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | 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 2 | Structural and Functional Characterization of the Human Thymidylate Synthase (hTS) Interface Variant R175C, New Perspectives for the Development of hTS Inhibitors. Molecules. 2019 Apr 7;24(7):1362. | ||||
| REF 3 | Evidence of Destabilization of the Human Thymidylate Synthase (hTS) Dimeric Structure Induced by the Interface Mutation Q62R. Biomolecules. 2019 Apr 3;9(4):134. | ||||
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