1HVY
Human thymidylate synthase complexed with dUMP and Raltitrexed, an antifolate drug, is in the closed conformation
Functional Information from GO Data
| Chain | GOid | namespace | contents |
| A | 0000900 | molecular_function | mRNA regulatory element binding translation repressor activity |
| A | 0004799 | molecular_function | thymidylate synthase activity |
| A | 0005542 | molecular_function | folic acid binding |
| A | 0005634 | cellular_component | nucleus |
| A | 0005737 | cellular_component | cytoplasm |
| A | 0005739 | cellular_component | mitochondrion |
| A | 0005743 | cellular_component | mitochondrial inner membrane |
| A | 0005759 | cellular_component | mitochondrial matrix |
| A | 0005829 | cellular_component | cytosol |
| A | 0006231 | biological_process | dTMP biosynthetic process |
| A | 0006235 | biological_process | dTTP biosynthetic process |
| A | 0008168 | molecular_function | methyltransferase activity |
| A | 0009165 | biological_process | nucleotide biosynthetic process |
| A | 0016020 | cellular_component | membrane |
| A | 0016740 | molecular_function | transferase activity |
| A | 0016741 | molecular_function | transferase activity, transferring one-carbon groups |
| A | 0017148 | biological_process | negative regulation of translation |
| A | 0032259 | biological_process | methylation |
| A | 0035999 | biological_process | tetrahydrofolate interconversion |
| A | 0046653 | biological_process | tetrahydrofolate metabolic process |
| A | 0071897 | biological_process | DNA biosynthetic process |
| A | 1990825 | molecular_function | sequence-specific mRNA binding |
| B | 0000900 | molecular_function | mRNA regulatory element binding translation repressor activity |
| B | 0004799 | molecular_function | thymidylate synthase activity |
| B | 0005542 | molecular_function | folic acid binding |
| B | 0005634 | cellular_component | nucleus |
| B | 0005737 | cellular_component | cytoplasm |
| B | 0005739 | cellular_component | mitochondrion |
| B | 0005743 | cellular_component | mitochondrial inner membrane |
| B | 0005759 | cellular_component | mitochondrial matrix |
| B | 0005829 | cellular_component | cytosol |
| B | 0006231 | biological_process | dTMP biosynthetic process |
| B | 0006235 | biological_process | dTTP biosynthetic process |
| B | 0008168 | molecular_function | methyltransferase activity |
| B | 0009165 | biological_process | nucleotide biosynthetic process |
| B | 0016020 | cellular_component | membrane |
| B | 0016740 | molecular_function | transferase activity |
| B | 0016741 | molecular_function | transferase activity, transferring one-carbon groups |
| B | 0017148 | biological_process | negative regulation of translation |
| B | 0032259 | biological_process | methylation |
| B | 0035999 | biological_process | tetrahydrofolate interconversion |
| B | 0046653 | biological_process | tetrahydrofolate metabolic process |
| B | 0071897 | biological_process | DNA biosynthetic process |
| B | 1990825 | molecular_function | sequence-specific mRNA binding |
| C | 0000900 | molecular_function | mRNA regulatory element binding translation repressor activity |
| C | 0004799 | molecular_function | thymidylate synthase activity |
| C | 0005542 | molecular_function | folic acid binding |
| C | 0005634 | cellular_component | nucleus |
| C | 0005737 | cellular_component | cytoplasm |
| C | 0005739 | cellular_component | mitochondrion |
| C | 0005743 | cellular_component | mitochondrial inner membrane |
| C | 0005759 | cellular_component | mitochondrial matrix |
| C | 0005829 | cellular_component | cytosol |
| C | 0006231 | biological_process | dTMP biosynthetic process |
| C | 0006235 | biological_process | dTTP biosynthetic process |
| C | 0008168 | molecular_function | methyltransferase activity |
| C | 0009165 | biological_process | nucleotide biosynthetic process |
| C | 0016020 | cellular_component | membrane |
| C | 0016740 | molecular_function | transferase activity |
| C | 0016741 | molecular_function | transferase activity, transferring one-carbon groups |
| C | 0017148 | biological_process | negative regulation of translation |
| C | 0032259 | biological_process | methylation |
| C | 0035999 | biological_process | tetrahydrofolate interconversion |
| C | 0046653 | biological_process | tetrahydrofolate metabolic process |
| C | 0071897 | biological_process | DNA biosynthetic process |
| C | 1990825 | molecular_function | sequence-specific mRNA binding |
| D | 0000900 | molecular_function | mRNA regulatory element binding translation repressor activity |
| D | 0004799 | molecular_function | thymidylate synthase activity |
| D | 0005542 | molecular_function | folic acid binding |
| D | 0005634 | cellular_component | nucleus |
| D | 0005737 | cellular_component | cytoplasm |
| D | 0005739 | cellular_component | mitochondrion |
| D | 0005743 | cellular_component | mitochondrial inner membrane |
| D | 0005759 | cellular_component | mitochondrial matrix |
| D | 0005829 | cellular_component | cytosol |
| D | 0006231 | biological_process | dTMP biosynthetic process |
| D | 0006235 | biological_process | dTTP biosynthetic process |
| D | 0008168 | molecular_function | methyltransferase activity |
| D | 0009165 | biological_process | nucleotide biosynthetic process |
| D | 0016020 | cellular_component | membrane |
| D | 0016740 | molecular_function | transferase activity |
| D | 0016741 | molecular_function | transferase activity, transferring one-carbon groups |
| D | 0017148 | biological_process | negative regulation of translation |
| D | 0032259 | biological_process | methylation |
| D | 0035999 | biological_process | tetrahydrofolate interconversion |
| D | 0046653 | biological_process | tetrahydrofolate metabolic process |
| D | 0071897 | biological_process | DNA biosynthetic process |
| D | 1990825 | molecular_function | sequence-specific mRNA binding |
Functional Information from PDB Data
| site_id | AC1 |
| Number of Residues | 18 |
| Details | BINDING SITE FOR RESIDUE D16 A 414 |
| Chain | Residue |
| A | PHE80 |
| A | MET311 |
| A | ALA312 |
| A | UMP314 |
| A | HOH435 |
| A | HOH477 |
| A | HOH548 |
| A | HOH980 |
| A | HOH985 |
| A | HOH1017 |
| A | GLU87 |
| A | ILE108 |
| A | TRP109 |
| A | ASP218 |
| A | LEU221 |
| A | GLY222 |
| A | PHE225 |
| A | TYR258 |
| site_id | AC2 |
| Number of Residues | 16 |
| Details | BINDING SITE FOR RESIDUE D16 B 415 |
| Chain | Residue |
| B | GLU87 |
| B | ILE108 |
| B | TRP109 |
| B | ASN112 |
| B | ASP218 |
| B | LEU221 |
| B | GLY222 |
| B | PHE225 |
| B | TYR258 |
| B | LYS308 |
| B | MET311 |
| B | ALA312 |
| B | UMP315 |
| B | HOH589 |
| B | HOH648 |
| B | HOH789 |
| site_id | AC3 |
| Number of Residues | 15 |
| Details | BINDING SITE FOR RESIDUE D16 C 416 |
| Chain | Residue |
| C | PHE80 |
| C | GLU87 |
| C | ILE108 |
| C | TRP109 |
| C | ASP218 |
| C | LEU221 |
| C | GLY222 |
| C | PHE225 |
| C | TYR258 |
| C | MET311 |
| C | UMP316 |
| C | HOH586 |
| C | HOH605 |
| C | HOH690 |
| C | HOH848 |
| site_id | AC4 |
| Number of Residues | 18 |
| Details | BINDING SITE FOR RESIDUE D16 D 417 |
| Chain | Residue |
| D | PHE80 |
| D | GLU87 |
| D | ILE108 |
| D | TRP109 |
| D | ASN112 |
| D | ASP218 |
| D | LEU221 |
| D | GLY222 |
| D | PHE225 |
| D | TYR258 |
| D | MET311 |
| D | ALA312 |
| D | UMP317 |
| D | HOH604 |
| D | HOH624 |
| D | HOH678 |
| D | HOH865 |
| D | HOH907 |
| site_id | AC5 |
| Number of Residues | 16 |
| Details | BINDING SITE FOR RESIDUE UMP A 314 |
| Chain | Residue |
| A | ARG50 |
| A | LEU192 |
| A | CYS195 |
| A | HIS196 |
| A | GLN214 |
| A | ARG215 |
| A | SER216 |
| A | GLY217 |
| A | ASP218 |
| A | ASN226 |
| A | HIS256 |
| A | TYR258 |
| A | D16414 |
| A | HOH485 |
| B | ARG175 |
| B | ARG176 |
| site_id | AC6 |
| Number of Residues | 18 |
| Details | BINDING SITE FOR RESIDUE UMP B 315 |
| Chain | Residue |
| B | HOH504 |
| B | HOH565 |
| A | ARG175 |
| A | ARG176 |
| B | ARG50 |
| B | LEU192 |
| B | CYS195 |
| B | HIS196 |
| B | GLN214 |
| B | ARG215 |
| B | SER216 |
| B | GLY217 |
| B | ASP218 |
| B | ASN226 |
| B | HIS256 |
| B | TYR258 |
| B | D16415 |
| B | HOH496 |
| site_id | AC7 |
| Number of Residues | 15 |
| Details | BINDING SITE FOR RESIDUE UMP C 316 |
| Chain | Residue |
| C | ARG50 |
| C | CYS195 |
| C | HIS196 |
| C | GLN214 |
| C | ARG215 |
| C | SER216 |
| C | GLY217 |
| C | ASP218 |
| C | ASN226 |
| C | HIS256 |
| C | TYR258 |
| C | D16416 |
| C | HOH672 |
| D | ARG175 |
| D | ARG176 |
| site_id | AC8 |
| Number of Residues | 17 |
| Details | BINDING SITE FOR RESIDUE UMP D 317 |
| Chain | Residue |
| C | ARG175 |
| C | ARG176 |
| D | ARG50 |
| D | TYR135 |
| D | CYS195 |
| D | HIS196 |
| D | GLN214 |
| D | ARG215 |
| D | SER216 |
| D | GLY217 |
| D | ASP218 |
| D | ASN226 |
| D | HIS256 |
| D | TYR258 |
| D | D16417 |
| D | HOH524 |
| D | HOH619 |
| site_id | AC9 |
| Number of Residues | 7 |
| Details | BINDING SITE FOR RESIDUE BME A 1514 |
| Chain | Residue |
| A | ARG163 |
| A | VAL164 |
| A | THR167 |
| A | ARG176 |
| A | ILE178 |
| A | HOH641 |
| A | HOH997 |
| site_id | BC1 |
| Number of Residues | 5 |
| Details | BINDING SITE FOR RESIDUE BME B 1515 |
| Chain | Residue |
| B | ARG163 |
| B | THR167 |
| B | ASP174 |
| B | ARG176 |
| B | ILE178 |
| site_id | BC2 |
| Number of Residues | 4 |
| Details | BINDING SITE FOR RESIDUE BME C 1516 |
| Chain | Residue |
| C | ARG163 |
| C | THR167 |
| C | ILE178 |
| C | HOH476 |
| site_id | BC3 |
| Number of Residues | 5 |
| Details | BINDING SITE FOR RESIDUE BME D 1517 |
| Chain | Residue |
| D | ARG163 |
| D | THR167 |
| D | ASP174 |
| D | ARG176 |
| D | ILE178 |
Functional Information from PROSITE/UniProt
| site_id | PS00091 |
| Number of Residues | 29 |
| Details | THYMIDYLATE_SYNTHASE Thymidylate synthase active site. RriImcaWNprdlplma.....LpPCHalcQFyV |
| Chain | Residue | Details |
| A | ARG175-VAL203 |
Functional Information from SwissProt/UniProt
| site_id | SWS_FT_FI1 |
| Number of Residues | 4 |
| Details | ACT_SITE: Nucleophile => ECO:0000250|UniProtKB:P0A884 |
| Chain | Residue | Details |
| A | HIS196 | |
| B | HIS196 | |
| C | HIS196 | |
| D | HIS196 |
| site_id | SWS_FT_FI2 |
| Number of Residues | 8 |
| Details | BINDING: in other chain => ECO:0000250|UniProtKB:P0A884 |
| Chain | Residue | Details |
| A | THR51 | |
| A | ILE227 | |
| B | THR51 | |
| B | ILE227 | |
| C | THR51 | |
| C | ILE227 | |
| D | THR51 | |
| D | ILE227 |
| site_id | SWS_FT_FI3 |
| Number of Residues | 4 |
| Details | BINDING: BINDING => ECO:0000250|UniProtKB:P45352 |
| Chain | Residue | Details |
| A | ARG176 | |
| B | ARG176 | |
| C | ARG176 | |
| D | ARG176 |
| site_id | SWS_FT_FI4 |
| Number of Residues | 12 |
| Details | BINDING: in other chain => ECO:0000250|UniProtKB:P45352 |
| Chain | Residue | Details |
| A | HIS196 | |
| D | HIS196 | |
| D | SER216 | |
| D | ILE257 | |
| A | SER216 | |
| A | ILE257 | |
| B | HIS196 | |
| B | SER216 | |
| B | ILE257 | |
| C | HIS196 | |
| C | SER216 | |
| C | ILE257 |
| site_id | SWS_FT_FI5 |
| Number of Residues | 8 |
| Details | BINDING: BINDING => ECO:0000250|UniProtKB:P0A884 |
| Chain | Residue | Details |
| A | MET219 | |
| A | VAL313 | |
| B | MET219 | |
| B | VAL313 | |
| C | MET219 | |
| C | VAL313 | |
| D | MET219 | |
| D | VAL313 |
| site_id | SWS_FT_FI6 |
| Number of Residues | 4 |
| Details | MOD_RES: Phosphoserine => ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163 |
| Chain | Residue | Details |
| A | ARG115 | |
| B | ARG115 | |
| C | ARG115 | |
| D | ARG115 |
| site_id | SWS_FT_FI7 |
| Number of Residues | 16 |
| Details | CROSSLNK: Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) => ECO:0007744|PubMed:28112733 |
| Chain | Residue | Details |
| A | ILE288 | |
| C | ALA293 | |
| C | MET309 | |
| D | ILE288 | |
| D | ALA293 | |
| D | MET309 | |
| A | ALA293 | |
| A | MET309 | |
| B | ILE288 | |
| B | ALA293 | |
| B | MET309 | |
| C | ILE288 |
Catalytic Information from CSA
| site_id | CSA1 |
| Number of Residues | 6 |
| Details | Annotated By Reference To The Literature 1b02 |
| Chain | Residue | Details |
| A | ASP254 | |
| A | SER216 | |
| A | CYS195 | |
| A | ASP218 | |
| A | GLU87 | |
| A | HIS256 |
| site_id | CSA2 |
| Number of Residues | 6 |
| Details | Annotated By Reference To The Literature 1b02 |
| Chain | Residue | Details |
| B | ASP254 | |
| B | SER216 | |
| B | CYS195 | |
| B | ASP218 | |
| B | GLU87 | |
| B | HIS256 |
| site_id | CSA3 |
| Number of Residues | 6 |
| Details | Annotated By Reference To The Literature 1b02 |
| Chain | Residue | Details |
| C | ASP254 | |
| C | SER216 | |
| C | CYS195 | |
| C | ASP218 | |
| C | GLU87 | |
| C | HIS256 |
| site_id | CSA4 |
| Number of Residues | 6 |
| Details | Annotated By Reference To The Literature 1b02 |
| Chain | Residue | Details |
| D | ASP254 | |
| D | SER216 | |
| D | CYS195 | |
| D | ASP218 | |
| D | GLU87 | |
| D | HIS256 |
| site_id | CSA5 |
| Number of Residues | 3 |
| Details | Annotated By Reference To The Literature 1b02 |
| Chain | Residue | Details |
| A | ASN226 | |
| A | SER229 | |
| A | CYS195 |
| site_id | CSA6 |
| Number of Residues | 3 |
| Details | Annotated By Reference To The Literature 1b02 |
| Chain | Residue | Details |
| B | ASN226 | |
| B | SER229 | |
| B | CYS195 |
| site_id | CSA7 |
| Number of Residues | 3 |
| Details | Annotated By Reference To The Literature 1b02 |
| Chain | Residue | Details |
| C | ASN226 | |
| C | SER229 | |
| C | CYS195 |
| site_id | CSA8 |
| Number of Residues | 3 |
| Details | Annotated By Reference To The Literature 1b02 |
| Chain | Residue | Details |
| D | ASN226 | |
| D | SER229 | |
| D | CYS195 |
