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 | 2'-deoxyuridylic acid | Ligand Info | |||
| Canonical SMILES | C1C(C(OC1N2C=CC(=O)NC2=O)COP(=O)(O)O)O | ||||
| InChI | 1S/C9H13N2O8P/c12-5-3-8(11-2-1-7(13)10-9(11)14)19-6(5)4-18-20(15,16)17/h1-2,5-6,8,12H,3-4H2,(H,10,13,14)(H2,15,16,17)/t5-,6+,8+/m0/s1 | ||||
| InChIKey | JSRLJPSBLDHEIO-SHYZEUOFSA-N | ||||
| PubChem Compound ID | 65063 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3HB8 Structures of Thymidylate Synthase R163K with Substrates and Inhibitors Show Subunit Asymmetry | ||||||
| Method | X-ray diffraction | Resolution | 2.74 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: 1JU6 Human Thymidylate Synthase Complex with dUMP and LY231514, A Pyrrolo(2,3-d)pyrimidine-based Antifolate | ||||||
| Method | X-ray diffraction | Resolution | 2.89 Å | Mutation | Yes | [2] |
| PDB Sequence |
HGELQYLGQI
37 QHILRCGVEK47 DDRTGTGTLS57 VFGMQARYSL67 RDEFPLLTTK77 RVFWKGVLEE 87 LLWFIKGSTN97 AKELSSKGVK107 IWDANGSRDF117 LDSLGFSTRE127 EGDLGPVYGF 137 QWRHFGAEYR147 DMESDYSGQG157 VDQLQRVIDT167 IKTNPDDRRI177 IMCAWNPRDL 187 PLMALPPCHA197 LCQFYVVNSE207 LSCQLYQRSG217 DMGLGVPFNI227 ASYALLTYMI 237 AHITGLKPGD247 FIHTLGDAHI257 YLNHIEPLKI267 QLQREPRPFP277 KLRILRKVEK 287 IDDFKAEDFQ297 IEGYNPHPTI307 KMEMAV
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| PDB ID: 1JUJ Human Thymidylate Synthase Bound to dUMP and LY231514, a Pyrrolo(2,3-d)pyrimidine-based Antifolate | ||||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | Yes | [2] |
| PDB Sequence |
HGELQYLGQI
37 QHILRCGVEK47 DDRTGTGTLS57 VFGMQARYSL67 RDEFPLLTTK77 RVFWKGVLEE 87 LLWFIKGSTN97 AKELSSKGVK107 IWDANGSRDF117 LDSLGFSTRE127 EGDLGPVYGF 137 QWRHFGAEYR147 DMESDYSGQG157 VDQLQRVIDT167 IKTNPDDRRI177 IMCAWNPRDL 187 PLMALPPCHA197 LCQFYVVNSE207 LSCQLYQRSG217 DMGLGVPFNI227 ASYALLTYMI 237 AHITGLKPGD247 FIHTLGDAHI257 YLNHIEPLKI267 QLQREPRPFP277 KLRILRKVEK 287 IDDFKAEDFQ297 IEGYNPHPTI307 KMEMAV
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| 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 | [3] |
| 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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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .UMP or .UMP2 or .UMP3 or :3UMP;style chemicals stick;color identity;select .A:50 or .A:135 or .A:193 or .A:195 or .A:196 or .A:214 or .A:215 or .A:216 or .A:217 or .A:218 or .A:222 or .A:223 or .A:226 or .A:256 or .A:258; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5X66 Human thymidylate synthase in complex with dUMP and methotrexate | ||||||
| Method | X-ray diffraction | Resolution | 1.99 Å | Mutation | No | [4] |
| 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 TIKMEMAV
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .UMP or .UMP2 or .UMP3 or :3UMP;style chemicals stick;color identity;select .A:50 or .A:193 or .A:195 or .A:196 or .A:214 or .A:215 or .A:216 or .A:217 or .A:218 or .A:222 or .A:223 or .A:226 or .A:256 or .A:258; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5X5D Human thymidylate synthase bound with dUMP | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [4] |
| 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 TIKMEMAV
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .UMP or .UMP2 or .UMP3 or :3UMP;style chemicals stick;color identity;select .A:193 or .A:195 or .A:196 or .A:214 or .A:215 or .A:216 or .A:217 or .A:218 or .A:222 or .A:223 or .A:226 or .A:256 or .A:258; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5X67 Human thymidylate synthase in complex with dUMP and nolatrexed | ||||||
| Method | X-ray diffraction | Resolution | 2.13 Å | Mutation | No | [4] |
| PDB Sequence |
HGELQYLGQI
37 QHILRCGVRK47 DDRTGTGTLS57 VFGMQARYSL67 RDEFPLLTTK77 RVFWKGVLEE 87 LLWFIKGSTN97 AKELSSKGVK107 IWDANGSRDF117 LDSLGFSTRE127 EGDLGPVYGF 137 QWRHFGAEYR147 DMESDYSGQG157 VDQLQRVIDT167 IKTNPDDRRI177 IMCAWNPRDL 187 PLMALPPCHA197 LCQFYVVNSE207 LSCQLYQRSG217 DMGLGVPFNI227 ASYALLTYMI 237 AHITGLKPGD247 FIHTLGDAHI257 YLNHIEPLKI267 QLQREPRPFP277 KLRILRKVEK 287 IDDFKAEDFQ297 IEGYNPHPTI307 KMEMAV
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .UMP or .UMP2 or .UMP3 or :3UMP;style chemicals stick;color identity;select .A:50 or .A:109 or .A:135 or .A:192 or .A:193 or .A:195 or .A:196 or .A:214 or .A:215 or .A:216 or .A:217 or .A:218 or .A:222 or .A:223 or .A:226 or .A:256 or .A:258; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6PF3 Crystal structure of human thymidylate synthase Delta (7-29) in complex with dUMP and 2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)-4-chlorobenzoic acid | ||||||
| Method | X-ray diffraction | Resolution | 2.39 Å | Mutation | No | [5] |
| PDB Sequence |
SELQYLGQIQ
38 HILRCGVRKD48 DRTGTGTLSV58 FGMQARYSLR68 DEFPLLTTKR78 VFWKGVLEEL 88 LWFIKGSTNA98 KELSSKGVKI108 WDANGSRDFL118 DSLGFSTREE128 GDLGPVYGFQ 138 WRHFGAEYRD148 MESDYSGQGV158 DQLQRVIDTI168 KTNPDDRRII178 MCAWNPRDLP 188 LMALPPCHAL198 CQFYVVNSEL208 SCQLYQRSGD218 MGLGVPFNIA228 SYALLTYMIA 238 HITGLKPGDF248 IHTLGDAHIY258 LNHIEPLKIQ268 LQREPRPFPK278 LRILRKVEKI 288 DDFKAEDFQI298 EGYNPHPTIK308 MEMAV
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .UMP or .UMP2 or .UMP3 or :3UMP;style chemicals stick;color identity;select .A:50 or .A:135 or .A:192 or .A:193 or .A:195 or .A:196 or .A:214 or .A:215 or .A:216 or .A:217 or .A:218 or .A:222 or .A:223 or .A:226 or .A:256 or .A:258; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6PF5 Crystal structure of human thymidylate synthase Delta (7-29) in complex with dUMP and 2-(2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)-4-methoxyphenyl)acetic acid | ||||||
| Method | X-ray diffraction | Resolution | 2.39 Å | Mutation | No | [5] |
| PDB Sequence |
SELQYLGQIQ
38 HILRCGVRKD48 DRTGTGTLSV58 FGMQARYSLR68 DEFPLLTTKR78 VFWKGVLEEL 88 LWFIKGSTNA98 KELSSKGVKI108 WDANGSRDFL118 DSLGFSTREE128 GDLGPVYGFQ 138 WRHFGAEYRD148 MESDYSGQGV158 DQLQRVIDTI168 KTNPDDRRII178 MCAWNPRDLP 188 LMALPPCHAL198 CQFYVVNSEL208 SCQLYQRSGD218 MGLGVPFNIA228 SYALLTYMIA 238 HITGLKPGDF248 IHTLGDAHIY258 LNHIEPLKIQ268 LQREPRPFPK278 LRILRKVEKI 288 DDFKAEDFQI298 EGYNPHPTIK308 MEMAV
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .UMP or .UMP2 or .UMP3 or :3UMP;style chemicals stick;color identity;select .A:50 or .A:109 or .A:135 or .A:192 or .A:193 or .A:195 or .A:196 or .A:214 or .A:215 or .A:216 or .A:217 or .A:218 or .A:222 or .A:223 or .A:226 or .A:256 or .A:258; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 1I00 CRYSTAL STRUCTURE OF HUMAN THYMIDYLATE SYNTHASE, TERNARY COMPLEX WITH DUMP AND TOMUDEX | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [6] |
| PDB Sequence |
SELQYLGQIQ
38 HILRCGVRKD48 DRTGTGTLSV58 FGMQARYSLR68 DEFPLLTTKR78 VFWKGVLEEL 88 LWFIKGSTNA98 KELSSKGVKI108 WDANGSRDFL118 DSLGFSTREE128 GDLGPVYGFQ 138 WRHFGAEYRD148 MESDYSGQGV158 DQLQRVIDTI168 KTNPDDRRII178 MCAWNPRDLP 188 LMALPPCHAL198 CQFYVVNSEL208 SCQLYQRSGD218 MGLGVPFNIA228 SYALLTYMIA 238 HITGLKPGDF248 IHTLGDAHIY258 LNHIEPLKIQ268 LQREPRPFPK278 LRILRKVEKI 288 DDFKAEDFQI298 EGYNPHPT
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .UMP or .UMP2 or .UMP3 or :3UMP;style chemicals stick;color identity;select .A:50 or .A:135 or .A:192 or .A:193 or .A:195 or .A:196 or .A:214 or .A:215 or .A:216 or .A:217 or .A:218 or .A:222 or .A:223 or .A:226 or .A:256 or .A:258; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6PF6 Crystal structure of TS-DHFR from Cryptosporidium hominis in complex with NADPH, FdUMP and 2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)terephthalic acid | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [5] |
| PDB Sequence |
SELQYLGQIQ
38 HILRCGVRKD48 DRTGTGTLSV58 FGMQARYSLR68 DEFPLLTTKR78 VFWKGVLEEL 88 LWFIKGSTNA98 KELSSKGVKI108 WDANGSRDFL118 DSLGFSTREE128 GDLGPVYGFQ 138 WRHFGAEYRD148 MESDYSGQGV158 DQLQRVIDTI168 KTNPDDRRII178 MCAWNPRDLP 188 LMALPPCHAL198 CQFYVVNSEL208 SCQLYQRSGD218 MGLGVPFNIA228 SYALLTYMIA 238 HITGLKPGDF248 IHTLGDAHIY258 LNHIEPLKIQ268 LQREPRPFPK278 LRILRKVEKI 288 DDFKAEDFQI298 EGYNPHPTIK308 MEMAV
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .UMP or .UMP2 or .UMP3 or :3UMP;style chemicals stick;color identity;select .B:50 or .B:109 or .B:135 or .B:192 or .B:193 or .B:195 or .B:196 or .B:214 or .B:215 or .B:216 or .B:217 or .B:218 or .B:222 or .B:223 or .B:226 or .B:256 or .B:258; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6OJV Crystal structure of human thymidylate synthase delta(7-29) in complex with dUMP and 2-amino-4-oxo-4,7-dihydro-pyrrolo[2,3-d]pyrimidine-methyl-phenyl-L-glutamic acid | ||||||
| Method | X-ray diffraction | Resolution | 2.59 Å | Mutation | No | [7] |
| PDB Sequence |
SELQYLGQIQ
38 HILRCGVRKD48 DRTGTGTLSV58 FGMQARYSLR68 DEFPLLTTKR78 VFWKGVLEEL 88 LWFIKGSTNA98 KELSSKGVKI108 WDANGSRDFL118 DSLGFSTREE128 GDLGPVYGFQ 138 WRHFGAEYRD148 MESDYSGQGV158 DQLQRVIDTI168 KTNPDDRRII178 MCAWNPRDLP 188 LMALPPCHAL198 CQFYVVNSEL208 SCQLYQRSGD218 MGLGVPFNIA228 SYALLTYMIA 238 HITGLKPGDF248 IHTLGDAHIY258 LNHIEPLKIQ268 LQREPRPFPK278 LRILRKVEKI 288 DDFKAEDFQI298 EGYNPHPTIK308 MEMAV
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .UMP or .UMP2 or .UMP3 or :3UMP;style chemicals stick;color identity;select .B:50 or .B:109 or .B:135 or .B:192 or .B:193 or .B:195 or .B:196 or .B:214 or .B:215 or .B:216 or .B:217 or .B:218 or .B:222 or .B:223 or .B:226 or .B:256 or .B:258; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5X69 Human thymidylate synthase with a fragment bound in the dimer interface | ||||||
| Method | X-ray diffraction | Resolution | 2.69 Å | Mutation | No | [4] |
| 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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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .UMP or .UMP2 or .UMP3 or :3UMP;style chemicals stick;color identity;select .A:50 or .A:135 or .A:193 or .A:195 or .A:196 or .A:214 or .A:215 or .A:216 or .A:217 or .A:218 or .A:222 or .A:223 or .A:226 or .A:256 or .A:258; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5X5Q Human thymidylate synthase complexed with dUMP and raltitrexed | ||||||
| Method | X-ray diffraction | Resolution | 2.79 Å | Mutation | No | [4] |
| 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 TIKMEM
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .UMP or .UMP2 or .UMP3 or :3UMP;style chemicals stick;color identity;select .A:50 or .A:109 or .A:135 or .A:193 or .A:195 or .A:196 or .A:214 or .A:215 or .A:216 or .A:217 or .A:218 or .A:222 or .A:223 or .A:226 or .A:256 or .A:258; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6PF4 Crystal structure of human thymidylate synthase Delta (7-29) in complex with dUMP and 2-(2-(4-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl)benzamido)phenyl)acetic acid | ||||||
| Method | X-ray diffraction | Resolution | 2.85 Å | Mutation | No | [5] |
| PDB Sequence |
SELQYLGQIQ
38 HILRCGVRKD48 DRTGTGTLSV58 FGMQARYSLR68 DEFPLLTTKR78 VFWKGVLEEL 88 LWFIKGSTNA98 KELSSKGVKI108 WDANGSRDFL118 DSLGFSTREE128 GDLGPVYGFQ 138 WRHFGAEYRD148 MESDYSGQGV158 DQLQRVIDTI168 KTNPDDRRII178 MCAWNPRDLP 188 LMALPPCHAL198 CQFYVVNSEL208 SCQLYQRSGD218 MGLGVPFNIA228 SYALLTYMIA 238 HITGLKPGDF248 IHTLGDAHIY258 LNHIEPLKIQ268 LQREPRPFPK278 LRILRKVEKI 288 DDFKAEDFQI298 EGYNPHPTIK308 MEMA
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .UMP or .UMP2 or .UMP3 or :3UMP;style chemicals stick;color identity;select .B:50 or .B:109 or .B:135 or .B:192 or .B:193 or .B:195 or .B:196 or .B:214 or .B:215 or .B:216 or .B:217 or .B:218 or .B:222 or .B:223 or .B:226 or .B:256 or .B:258; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6OJU Crystal structure of human thymidylate synthase Delta (7-29) in complex with dUMP and 2-amino-4-oxo-4,7-dihydro-pyrrolo[2,3-d]pyrimidine-methyl-phenyl-D-glutamic acid | ||||||
| Method | X-ray diffraction | Resolution | 2.88 Å | Mutation | No | [7] |
| PDB Sequence |
SELQYLGQIQ
38 HILRCGVRKD48 DRTGTGTLSV58 FGMQARYSLR68 DEFPLLTTKR78 VFWKGVLEEL 88 LWFIKGSTNA98 KELSSKGVKI108 WDANGSRDFL118 DSLGFSTREE128 GDLGPVYGFQ 138 WRHFGAEYRD148 MESDYSGQGV158 DQLQRVIDTI168 KTNPDDRRII178 MCAWNPRDLP 188 LMALPPCHAL198 CQFYVVNSEL208 SCQLYQRSGD218 MGLGVPFNIA228 SYALLTYMIA 238 HITGLKPGDF248 IHTLGDAHIY258 LNHIEPLKIQ268 LQREPRPFPK278 LRILRKVEKI 288 DDFKAEDFQI298 EGYNPHPTIK308 MEMAV
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .UMP or .UMP2 or .UMP3 or :3UMP;style chemicals stick;color identity;select .B:50 or .B:109 or .B:135 or .B:192 or .B:193 or .B:195 or .B:196 or .B:214 or .B:215 or .B:216 or .B:217 or .B:218 or .B:222 or .B:223 or .B:226 or .B:256 or .B:258; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 5HS3 Human thymidylate synthase complexed with dUMP and 3-amino-2-benzoyl-4-methylthieno[2,3-b]pyridin-6-ol | ||||||
| Method | X-ray diffraction | Resolution | 3.10 Å | Mutation | No | [8] |
| PDB Sequence |
MPPHGELQYL
34 GQIQHILRCG44 VRKDDRTGTG54 TLSVFGMQAR64 YSLRDEFPLL74 TTKRVFWKGV 84 LEELLWFIKG94 STNAKELSSK104 GVKIWDANGS114 RDFLDSLGFS124 TREEGDLGPV 134 YGFQWRHFGA144 EYRDMESDYS154 GQGVDQLQRV164 IDTIKTNPDD174 RRIIMCAWNP 184 RDLPLMALPP194 CHALCQFYVV204 NSELSCQLYQ214 RSGDMGLGVP224 FNIASYALLT 234 YMIAHITGLK244 PGDFIHTLGD254 AHIYLNHIEP264 LKIQLQREPR274 PFPKLRILRK 284 VEKIDDFKAE294 DFQIEGYNPH304 PTIKMEMAV
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .UMP or .UMP2 or .UMP3 or :3UMP;style chemicals stick;color identity;select .A:50 or .A:109 or .A:135 or .A:192 or .A:193 or .A:195 or .A:196 or .A:214 or .A:215 or .A:216 or .A:217 or .A:218 or .A:222 or .A:223 or .A:226 or .A:256 or .A:258; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 1HVY Human thymidylate synthase complexed with dUMP and Raltitrexed, an antifolate drug, is in the closed conformation | ||||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | Yes | [9] |
| 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 IKMEMAV
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Click to Show 3D Structure of This Binding Site
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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 | Multi-targeted antifolates aimed at avoiding drug resistance form covalent closed inhibitory complexes with human and Escherichia coli thymidylate synthases. J Mol Biol. 2001 Nov 2;313(4):813-29. | ||||
| REF 3 | 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 4 | Structural analyses of human thymidylate synthase reveal a site that may control conformational switching between active and inactive states. J Biol Chem. 2017 Aug 11;292(32):13449-13458. | ||||
| REF 5 | Structure activity relationship towards design of cryptosporidium specific thymidylate synthase inhibitors. Eur J Med Chem. 2019 Dec 1;183:111673. | ||||
| REF 6 | Crystal structure of a deletion mutant of human thymidylate synthase Delta (7-29) and its ternary complex with Tomudex and dUMP. Protein Sci. 2001 May;10(5):988-96. | ||||
| REF 7 | Understanding the structural basis of species selective, stereospecific inhibition for Cryptosporidium and human thymidylate synthase. FEBS Lett. 2019 Aug;593(15):2069-2078. | ||||
| REF 8 | CETSA screening identifies known and novel thymidylate synthase inhibitors and slow intracellular activation of 5-fluorouracil. Nat Commun. 2016 Mar 24;7:11040. | ||||
| REF 9 | Human thymidylate synthase is in the closed conformation when complexed with dUMP and raltitrexed, an antifolate drug. Biochemistry. 2001 Feb 20;40(7):1897-902. | ||||
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