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 | Levoleucovorin | Ligand Info | |||
| Canonical SMILES | C1C(N(C2=C(N1)N=C(NC2=O)N)C=O)CNC3=CC=C(C=C3)C(=O)NC(CCC(=O)O)C(=O)O | ||||
| InChI | 1S/C20H23N7O7/c21-20-25-16-15(18(32)26-20)27(9-28)12(8-23-16)7-22-11-3-1-10(2-4-11)17(31)24-13(19(33)34)5-6-14(29)30/h1-4,9,12-13,22H,5-8H2,(H,24,31)(H,29,30)(H,33,34)(H4,21,23,25,26,32)/t12-,13-/m0/s1 | ||||
| InChIKey | VVIAGPKUTFNRDU-STQMWFEESA-N | ||||
| PubChem Compound ID | 135398559 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6QYQ Crystal structure of human thymidylate synthase (hTS) variant R175C | ||||||
| Method | X-ray diffraction | Resolution | 2.25 Å | Mutation | Yes | [1] |
| PDB Sequence |
> 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
|
|||||
|
|
LYS77[B]
4.632
ARG78[B]
4.817
PHE80[B]
3.389
GLU87[B]
4.848
ILE108[B]
3.309
TRP109[B]
3.870
ASN112[B]
3.106
LEU192[B]
3.272
HIS196[B]
3.876
ASP218[B]
2.793
LEU221[B]
3.369
GLY222[B]
3.120
VAL223[B]
4.869
PHE225[B]
3.672
ASN226[B]
3.538
TYR258[B]
4.309
ILE307[B]
4.411
MET309[B]
4.885
MET311[B]
3.237
ALA312[B]
3.121
LYS77[D]
4.723
PHE80[D]
3.587
GLU87[D]
4.703
ILE108[D]
3.564
TRP109[D]
3.947
ASN112[D]
2.902
LEU192[D]
3.289
HIS196[D]
4.001
ASP218[D]
2.824
LEU221[D]
3.278
GLY222[D]
3.186
PHE225[D]
3.535
ASN226[D]
3.211
TYR258[D]
4.475
ILE307[D]
4.442
MET309[D]
4.939
MET311[D]
3.252
ALA312[D]
3.147
|
|||||
| PDB ID: 6R2E Crystal structure of the human thymidylate synthase (hTS) interface variant Q62R | ||||||
| Method | X-ray diffraction | Resolution | 2.55 Å | Mutation | Yes | [2] |
| 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
|
|||||
|
|
LYS77[A]
4.581
PHE80[A]
3.306
GLU87[A]
4.521
LYS107[A]
4.940
ILE108[A]
3.579
TRP109[A]
3.238
ASN112[A]
2.773
TYR135[A]
4.675
LEU192[A]
3.432
HIS196[A]
4.260
ASP218[A]
2.807
LEU221[A]
3.144
GLY222[A]
3.226
PHE225[A]
3.388
ASN226[A]
3.049
TYR258[A]
3.806
ILE307[A]
4.350
MET309[A]
4.794
MET311[A]
2.851
ALA312[A]
3.300
LYS77[E]
4.676
PHE80[E]
3.403
GLU87[E]
4.296
LYS107[E]
4.975
ILE108[E]
3.570
TRP109[E]
3.255
ASN112[E]
2.990
TYR135[E]
3.896
LEU192[E]
3.707
HIS196[E]
4.159
ASP218[E]
2.845
LEU221[E]
3.457
GLY222[E]
3.009
PHE225[E]
3.318
ASN226[E]
3.868
TYR258[E]
4.096
ILE307[E]
4.333
MET309[E]
4.852
MET311[E]
2.809
ALA312[E]
2.966
|
|||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | 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 2 | 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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