3HBB
Structures of dihydrofolate reductase-thymidylate synthase of Trypanosoma cruzi in the folate-free state and in complex with two antifolate drugs, trimetrexate and methotrexate
Functional Information from GO Data
| Chain | GOid | namespace | contents |
| A | 0004146 | molecular_function | dihydrofolate reductase activity |
| A | 0004799 | molecular_function | thymidylate synthase activity |
| A | 0005739 | cellular_component | mitochondrion |
| A | 0005829 | cellular_component | cytosol |
| A | 0006231 | biological_process | dTMP biosynthetic process |
| A | 0006730 | biological_process | one-carbon metabolic process |
| A | 0008168 | molecular_function | methyltransferase activity |
| A | 0009165 | biological_process | nucleotide biosynthetic process |
| A | 0016491 | molecular_function | oxidoreductase activity |
| A | 0016741 | molecular_function | transferase activity, transferring one-carbon groups |
| A | 0032259 | biological_process | methylation |
| A | 0046654 | biological_process | tetrahydrofolate biosynthetic process |
| B | 0004146 | molecular_function | dihydrofolate reductase activity |
| B | 0004799 | molecular_function | thymidylate synthase activity |
| B | 0005739 | cellular_component | mitochondrion |
| B | 0005829 | cellular_component | cytosol |
| B | 0006231 | biological_process | dTMP biosynthetic process |
| B | 0006730 | biological_process | one-carbon metabolic process |
| B | 0008168 | molecular_function | methyltransferase activity |
| B | 0009165 | biological_process | nucleotide biosynthetic process |
| B | 0016491 | molecular_function | oxidoreductase activity |
| B | 0016741 | molecular_function | transferase activity, transferring one-carbon groups |
| B | 0032259 | biological_process | methylation |
| B | 0046654 | biological_process | tetrahydrofolate biosynthetic process |
| C | 0004146 | molecular_function | dihydrofolate reductase activity |
| C | 0004799 | molecular_function | thymidylate synthase activity |
| C | 0005739 | cellular_component | mitochondrion |
| C | 0005829 | cellular_component | cytosol |
| C | 0006231 | biological_process | dTMP biosynthetic process |
| C | 0006730 | biological_process | one-carbon metabolic process |
| C | 0008168 | molecular_function | methyltransferase activity |
| C | 0009165 | biological_process | nucleotide biosynthetic process |
| C | 0016491 | molecular_function | oxidoreductase activity |
| C | 0016741 | molecular_function | transferase activity, transferring one-carbon groups |
| C | 0032259 | biological_process | methylation |
| C | 0046654 | biological_process | tetrahydrofolate biosynthetic process |
| D | 0004146 | molecular_function | dihydrofolate reductase activity |
| D | 0004799 | molecular_function | thymidylate synthase activity |
| D | 0005739 | cellular_component | mitochondrion |
| D | 0005829 | cellular_component | cytosol |
| D | 0006231 | biological_process | dTMP biosynthetic process |
| D | 0006730 | biological_process | one-carbon metabolic process |
| D | 0008168 | molecular_function | methyltransferase activity |
| D | 0009165 | biological_process | nucleotide biosynthetic process |
| D | 0016491 | molecular_function | oxidoreductase activity |
| D | 0016741 | molecular_function | transferase activity, transferring one-carbon groups |
| D | 0032259 | biological_process | methylation |
| D | 0046654 | biological_process | tetrahydrofolate biosynthetic process |
Functional Information from PDB Data
| site_id | AC1 |
| Number of Residues | 23 |
| Details | BINDING SITE FOR RESIDUE NAP A 601 |
| Chain | Residue |
| A | VAL27 |
| A | LYS79 |
| A | THR80 |
| A | LEU99 |
| A | SER100 |
| A | SER101 |
| A | THR102 |
| A | GLY130 |
| A | GLY131 |
| A | ILE154 |
| A | GLY156 |
| A | ALA28 |
| A | GLY157 |
| A | SER158 |
| A | TYR160 |
| A | TMQ611 |
| A | ILE35 |
| A | GLY38 |
| A | ARG39 |
| A | SER40 |
| A | ILE41 |
| A | GLY77 |
| A | ARG78 |
| site_id | AC2 |
| Number of Residues | 12 |
| Details | BINDING SITE FOR RESIDUE TMQ A 611 |
| Chain | Residue |
| A | VAL26 |
| A | VAL27 |
| A | ALA28 |
| A | ILE41 |
| A | ASP48 |
| A | MET49 |
| A | PHE52 |
| A | ILE84 |
| A | PRO85 |
| A | LEU91 |
| A | ILE154 |
| A | NAP601 |
| site_id | AC3 |
| Number of Residues | 4 |
| Details | BINDING SITE FOR RESIDUE SO4 A 701 |
| Chain | Residue |
| A | ARG383 |
| A | ARG384 |
| D | ARG423 |
| D | SER424 |
| site_id | AC4 |
| Number of Residues | 3 |
| Details | BINDING SITE FOR RESIDUE SO4 A 805 |
| Chain | Residue |
| A | ARG39 |
| A | ARG78 |
| A | LYS79 |
| site_id | AC5 |
| Number of Residues | 5 |
| Details | BINDING SITE FOR RESIDUE SO4 A 813 |
| Chain | Residue |
| A | ARG249 |
| A | GLU250 |
| B | TRP206 |
| B | ARG208 |
| B | LEU230 |
| site_id | AC6 |
| Number of Residues | 3 |
| Details | BINDING SITE FOR RESIDUE SO4 A 814 |
| Chain | Residue |
| A | ARG323 |
| A | GLU335 |
| A | GLU336 |
| site_id | AC7 |
| Number of Residues | 2 |
| Details | BINDING SITE FOR RESIDUE SO4 A 815 |
| Chain | Residue |
| A | PHE288 |
| A | ARG290 |
| site_id | AC8 |
| Number of Residues | 2 |
| Details | BINDING SITE FOR RESIDUE SO4 A 817 |
| Chain | Residue |
| A | ARG233 |
| A | ARG235 |
| site_id | AC9 |
| Number of Residues | 2 |
| Details | BINDING SITE FOR RESIDUE EDO A 902 |
| Chain | Residue |
| A | TRP206 |
| B | EDO906 |
| site_id | BC1 |
| Number of Residues | 4 |
| Details | BINDING SITE FOR RESIDUE EDO A 904 |
| Chain | Residue |
| A | SER212 |
| A | TYR226 |
| B | VAL253 |
| B | SER467 |
| site_id | BC2 |
| Number of Residues | 23 |
| Details | BINDING SITE FOR RESIDUE NAP B 602 |
| Chain | Residue |
| B | ALA28 |
| B | ILE35 |
| B | ARG39 |
| B | SER40 |
| B | ILE41 |
| B | GLY77 |
| B | ARG78 |
| B | LYS79 |
| B | THR80 |
| B | LEU99 |
| B | SER100 |
| B | SER101 |
| B | THR102 |
| B | GLY130 |
| B | GLY131 |
| B | ILE154 |
| B | GLY155 |
| B | GLY156 |
| B | GLY157 |
| B | SER158 |
| B | VAL159 |
| B | TYR160 |
| B | TMQ612 |
| site_id | BC3 |
| Number of Residues | 7 |
| Details | BINDING SITE FOR RESIDUE TMQ B 612 |
| Chain | Residue |
| B | ASP48 |
| B | PHE52 |
| B | SER83 |
| B | ILE154 |
| B | HOH549 |
| B | HOH558 |
| B | NAP602 |
| site_id | BC4 |
| Number of Residues | 3 |
| Details | BINDING SITE FOR RESIDUE SO4 B 806 |
| Chain | Residue |
| B | ARG323 |
| B | GLU335 |
| B | GLU336 |
| site_id | BC5 |
| Number of Residues | 4 |
| Details | BINDING SITE FOR RESIDUE SO4 B 809 |
| Chain | Residue |
| B | ARG491 |
| B | ARG493 |
| B | GLU494 |
| B | ASP498 |
| site_id | BC6 |
| Number of Residues | 2 |
| Details | BINDING SITE FOR RESIDUE SO4 B 818 |
| Chain | Residue |
| B | GLN364 |
| B | GLY365 |
| site_id | BC7 |
| Number of Residues | 2 |
| Details | BINDING SITE FOR RESIDUE SO4 B 821 |
| Chain | Residue |
| B | ARG233 |
| B | ARG235 |
| site_id | BC8 |
| Number of Residues | 2 |
| Details | BINDING SITE FOR RESIDUE SO4 B 823 |
| Chain | Residue |
| B | PHE288 |
| B | ARG290 |
| site_id | BC9 |
| Number of Residues | 5 |
| Details | BINDING SITE FOR RESIDUE EDO B 906 |
| Chain | Residue |
| A | ARG177 |
| A | EDO902 |
| B | ASN252 |
| B | VAL253 |
| C | ASN413 |
| site_id | CC1 |
| Number of Residues | 5 |
| Details | BINDING SITE FOR RESIDUE SO4 C 702 |
| Chain | Residue |
| B | ARG383 |
| B | ARG384 |
| C | ARG257 |
| C | ARG423 |
| C | SER424 |
| site_id | CC2 |
| Number of Residues | 23 |
| Details | BINDING SITE FOR RESIDUE NAP C 603 |
| Chain | Residue |
| C | ALA28 |
| C | ILE35 |
| C | GLY38 |
| C | ARG39 |
| C | SER40 |
| C | ILE41 |
| C | GLY77 |
| C | ARG78 |
| C | LYS79 |
| C | THR80 |
| C | LEU99 |
| C | SER100 |
| C | SER101 |
| C | THR102 |
| C | GLY130 |
| C | GLY131 |
| C | ILE154 |
| C | GLY156 |
| C | GLY157 |
| C | SER158 |
| C | VAL159 |
| C | TYR160 |
| C | TMQ613 |
| site_id | CC3 |
| Number of Residues | 10 |
| Details | BINDING SITE FOR RESIDUE TMQ C 613 |
| Chain | Residue |
| C | VAL26 |
| C | VAL27 |
| C | ASP48 |
| C | MET49 |
| C | PHE52 |
| C | SER83 |
| C | ILE84 |
| C | PRO85 |
| C | ILE154 |
| C | NAP603 |
| site_id | CC4 |
| Number of Residues | 5 |
| Details | BINDING SITE FOR RESIDUE SO4 C 703 |
| Chain | Residue |
| B | ARG257 |
| B | ARG423 |
| C | ARG383 |
| C | ARG384 |
| C | HOH565 |
| site_id | CC5 |
| Number of Residues | 2 |
| Details | BINDING SITE FOR RESIDUE SO4 C 802 |
| Chain | Residue |
| C | ARG60 |
| C | EDO908 |
| site_id | CC6 |
| Number of Residues | 3 |
| Details | BINDING SITE FOR RESIDUE SO4 C 807 |
| Chain | Residue |
| C | ARG39 |
| C | ARG78 |
| C | LYS79 |
| site_id | CC7 |
| Number of Residues | 7 |
| Details | BINDING SITE FOR RESIDUE SO4 C 808 |
| Chain | Residue |
| B | GLY351 |
| B | ASN391 |
| B | SER393 |
| C | PHE350 |
| C | GLY351 |
| C | ASN391 |
| C | SER393 |
| site_id | CC8 |
| Number of Residues | 3 |
| Details | BINDING SITE FOR RESIDUE SO4 C 812 |
| Chain | Residue |
| C | PHE288 |
| C | ARG290 |
| C | EDO909 |
| site_id | CC9 |
| Number of Residues | 2 |
| Details | BINDING SITE FOR RESIDUE SO4 C 816 |
| Chain | Residue |
| C | ARG233 |
| C | ARG235 |
| site_id | DC1 |
| Number of Residues | 4 |
| Details | BINDING SITE FOR RESIDUE SO4 C 822 |
| Chain | Residue |
| C | ARG491 |
| C | ARG493 |
| C | GLU494 |
| C | ASP498 |
| site_id | DC2 |
| Number of Residues | 3 |
| Details | BINDING SITE FOR RESIDUE SO4 C 824 |
| Chain | Residue |
| C | ARG323 |
| C | GLU335 |
| C | GLU336 |
| site_id | DC3 |
| Number of Residues | 4 |
| Details | BINDING SITE FOR RESIDUE EDO C 908 |
| Chain | Residue |
| C | ARG286 |
| C | VAL506 |
| C | TYR509 |
| C | SO4802 |
| site_id | DC4 |
| Number of Residues | 4 |
| Details | BINDING SITE FOR RESIDUE EDO C 909 |
| Chain | Residue |
| C | VAL287 |
| C | PHE288 |
| C | HOH569 |
| C | SO4812 |
| site_id | DC5 |
| Number of Residues | 4 |
| Details | BINDING SITE FOR RESIDUE EDO C 910 |
| Chain | Residue |
| C | GLN173 |
| C | ALA174 |
| C | LYS229 |
| C | ILE231 |
| site_id | DC6 |
| Number of Residues | 7 |
| Details | BINDING SITE FOR RESIDUE EDO C 912 |
| Chain | Residue |
| B | ASN413 |
| C | ASN252 |
| C | VAL253 |
| D | ARG177 |
| D | ARG208 |
| D | HOH552 |
| D | EDO911 |
| site_id | DC7 |
| Number of Residues | 24 |
| Details | BINDING SITE FOR RESIDUE NAP D 604 |
| Chain | Residue |
| D | ALA28 |
| D | ILE35 |
| D | GLY38 |
| D | ARG39 |
| D | SER40 |
| D | ILE41 |
| D | GLY77 |
| D | ARG78 |
| D | LYS79 |
| D | THR80 |
| D | LEU99 |
| D | SER100 |
| D | SER101 |
| D | THR102 |
| D | GLY130 |
| D | GLY131 |
| D | ILE154 |
| D | GLY155 |
| D | GLY156 |
| D | GLY157 |
| D | SER158 |
| D | VAL159 |
| D | TYR160 |
| D | TMQ614 |
| site_id | DC8 |
| Number of Residues | 9 |
| Details | BINDING SITE FOR RESIDUE TMQ D 614 |
| Chain | Residue |
| D | VAL26 |
| D | VAL27 |
| D | ALA28 |
| D | ASP48 |
| D | MET49 |
| D | PHE52 |
| D | PRO85 |
| D | ILE154 |
| D | NAP604 |
| site_id | DC9 |
| Number of Residues | 5 |
| Details | BINDING SITE FOR RESIDUE SO4 D 704 |
| Chain | Residue |
| A | ARG257 |
| A | ARG423 |
| A | SER424 |
| D | ARG383 |
| D | ARG384 |
| site_id | EC1 |
| Number of Residues | 2 |
| Details | BINDING SITE FOR RESIDUE SO4 D 801 |
| Chain | Residue |
| D | ARG60 |
| D | TYR509 |
| site_id | EC2 |
| Number of Residues | 2 |
| Details | BINDING SITE FOR RESIDUE SO4 D 803 |
| Chain | Residue |
| D | PHE288 |
| D | ARG290 |
| site_id | EC3 |
| Number of Residues | 2 |
| Details | BINDING SITE FOR RESIDUE SO4 D 804 |
| Chain | Residue |
| D | ARG482 |
| D | PRO513 |
| site_id | EC4 |
| Number of Residues | 2 |
| Details | BINDING SITE FOR RESIDUE SO4 D 810 |
| Chain | Residue |
| D | ARG491 |
| D | ARG493 |
| site_id | EC5 |
| Number of Residues | 3 |
| Details | BINDING SITE FOR RESIDUE SO4 D 811 |
| Chain | Residue |
| D | ARG323 |
| D | GLU335 |
| D | GLU336 |
| site_id | EC6 |
| Number of Residues | 1 |
| Details | BINDING SITE FOR RESIDUE SO4 D 819 |
| Chain | Residue |
| D | ARG78 |
| site_id | EC7 |
| Number of Residues | 2 |
| Details | BINDING SITE FOR RESIDUE SO4 D 820 |
| Chain | Residue |
| D | ARG233 |
| D | ARG235 |
| site_id | EC8 |
| Number of Residues | 5 |
| Details | BINDING SITE FOR RESIDUE EDO D 901 |
| Chain | Residue |
| C | SER467 |
| D | ILE211 |
| D | SER212 |
| D | GLU214 |
| D | TYR226 |
| site_id | EC9 |
| Number of Residues | 7 |
| Details | BINDING SITE FOR RESIDUE EDO D 903 |
| Chain | Residue |
| C | ARG177 |
| C | TRP206 |
| C | ARG208 |
| D | ARG249 |
| D | GLU250 |
| D | GLY251 |
| D | EDO905 |
| site_id | FC1 |
| Number of Residues | 5 |
| Details | BINDING SITE FOR RESIDUE EDO D 905 |
| Chain | Residue |
| C | ARG177 |
| C | ARG208 |
| D | ASN252 |
| D | VAL253 |
| D | EDO903 |
| site_id | FC2 |
| Number of Residues | 6 |
| Details | BINDING SITE FOR RESIDUE EDO D 907 |
| Chain | Residue |
| C | ILE211 |
| C | SER212 |
| C | GLU214 |
| D | HIS255 |
| D | GLY261 |
| D | SER467 |
| site_id | FC3 |
| Number of Residues | 4 |
| Details | BINDING SITE FOR RESIDUE EDO D 911 |
| Chain | Residue |
| C | ARG249 |
| C | EDO912 |
| D | TRP206 |
| D | ARG208 |
Functional Information from PROSITE/UniProt
| site_id | PS00075 |
| Number of Residues | 23 |
| Details | DHFR_1 Dihydrofolate reductase (DHFR) domain signature. GIGdgrsIPWnvpe.DmkfFrdvT |
| Chain | Residue | Details |
| A | GLY34-THR56 |
| site_id | PS00091 |
| Number of Residues | 29 |
| Details | THYMIDYLATE_SYNTHASE Thymidylate synthase active site. RrmLftaWNpsalprma.....LpPCHllaQFyV |
| Chain | Residue | Details |
| A | ARG383-VAL411 |
Functional Information from SwissProt/UniProt
| site_id | SWS_FT_FI1 |
| Number of Residues | 4 |
| Details | ACT_SITE: ACT_SITE => ECO:0000250 |
| Chain | Residue | Details |
| A | CYS403 | |
| B | CYS403 | |
| C | CYS403 | |
| D | CYS403 |
| site_id | SWS_FT_FI2 |
| Number of Residues | 60 |
| Details | BINDING: |
| Chain | Residue | Details |
| A | TYR160 | |
| A | THR178 | |
| A | ARG257 | |
| A | HIS404 | |
| A | GLN422 | |
| A | ASN434 | |
| A | HIS464 | |
| B | VAL26 | |
| B | ALA28 | |
| B | GLY34 | |
| B | ASP48 | |
| B | ARG78 | |
| B | LEU99 | |
| B | ILE154 | |
| B | GLY155 | |
| B | TYR160 | |
| B | THR178 | |
| B | ARG257 | |
| B | HIS404 | |
| B | GLN422 | |
| B | ASN434 | |
| B | HIS464 | |
| C | VAL26 | |
| C | ALA28 | |
| C | GLY34 | |
| C | ASP48 | |
| C | ARG78 | |
| C | LEU99 | |
| C | ILE154 | |
| C | GLY155 | |
| C | TYR160 | |
| C | THR178 | |
| C | ARG257 | |
| C | HIS404 | |
| C | GLN422 | |
| C | ASN434 | |
| C | HIS464 | |
| D | VAL26 | |
| D | ALA28 | |
| D | GLY34 | |
| D | ASP48 | |
| D | ARG78 | |
| D | LEU99 | |
| D | ILE154 | |
| D | GLY155 | |
| D | TYR160 | |
| D | THR178 | |
| D | ARG257 | |
| D | HIS404 | |
| D | GLN422 | |
| D | ASN434 | |
| D | HIS464 | |
| A | VAL26 | |
| A | ALA28 | |
| A | GLY34 | |
| A | ASP48 | |
| A | ARG78 | |
| A | LEU99 | |
| A | ILE154 | |
| A | GLY155 |
