5T7O
Crystal structure of Trypanosoma cruzi Dihydrofolate Reductase-Thymidylate Synthase in complex with (6S)-5,6,7,8-TETRAHYDROFOLATE
Functional Information from GO Data
| Chain | GOid | namespace | contents |
| A | 0000166 | molecular_function | nucleotide binding |
| A | 0003824 | molecular_function | catalytic activity |
| 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 | 0016740 | molecular_function | transferase activity |
| A | 0016741 | molecular_function | transferase activity, transferring one-carbon groups |
| A | 0032259 | biological_process | methylation |
| A | 0046654 | biological_process | tetrahydrofolate biosynthetic process |
| B | 0000166 | molecular_function | nucleotide binding |
| B | 0003824 | molecular_function | catalytic activity |
| 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 | 0016740 | molecular_function | transferase activity |
| B | 0016741 | molecular_function | transferase activity, transferring one-carbon groups |
| B | 0032259 | biological_process | methylation |
| B | 0046654 | biological_process | tetrahydrofolate biosynthetic process |
| C | 0000166 | molecular_function | nucleotide binding |
| C | 0003824 | molecular_function | catalytic activity |
| 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 | 0016740 | molecular_function | transferase activity |
| C | 0016741 | molecular_function | transferase activity, transferring one-carbon groups |
| C | 0032259 | biological_process | methylation |
| C | 0046654 | biological_process | tetrahydrofolate biosynthetic process |
| D | 0000166 | molecular_function | nucleotide binding |
| D | 0003824 | molecular_function | catalytic activity |
| 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 | 0016740 | molecular_function | transferase 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 | 30 |
| Details | binding site for residue NAP A 701 |
| Chain | Residue |
| A | ALA28 |
| A | SER100 |
| A | SER101 |
| A | THR102 |
| A | GLY130 |
| A | GLY131 |
| A | GLY156 |
| A | GLY157 |
| A | SER158 |
| A | VAL159 |
| A | TYR160 |
| A | ILE35 |
| A | THG702 |
| A | HOH807 |
| A | HOH900 |
| A | HOH922 |
| A | HOH928 |
| A | HOH948 |
| A | HOH1021 |
| A | HOH1053 |
| A | HOH1080 |
| A | HOH1094 |
| A | GLY36 |
| A | HOH1110 |
| A | GLY77 |
| A | ARG78 |
| A | LYS79 |
| A | THR80 |
| A | SER83 |
| A | LEU99 |
| site_id | AC2 |
| Number of Residues | 21 |
| Details | binding site for residue THG A 702 |
| Chain | Residue |
| A | VAL26 |
| A | VAL27 |
| A | ALA28 |
| A | ASP48 |
| A | MET49 |
| A | PHE52 |
| A | ARG53 |
| A | ILE84 |
| A | PRO85 |
| A | PHE88 |
| A | LEU91 |
| A | ARG94 |
| A | ILE154 |
| A | TYR160 |
| A | THR178 |
| A | NAP701 |
| A | HOH807 |
| A | HOH830 |
| A | HOH1001 |
| A | HOH1021 |
| A | HOH1123 |
| site_id | AC3 |
| Number of Residues | 15 |
| Details | binding site for residue UMP A 703 |
| Chain | Residue |
| A | CYS403 |
| A | HIS404 |
| A | GLN422 |
| A | ARG423 |
| A | SER424 |
| A | ASP426 |
| A | GLY430 |
| A | ASN434 |
| A | HIS464 |
| A | TYR466 |
| A | HOH802 |
| A | HOH997 |
| A | HOH1093 |
| B | ARG383 |
| B | ARG384 |
| site_id | AC4 |
| Number of Residues | 5 |
| Details | binding site for residue EDO A 704 |
| Chain | Residue |
| A | ALA140 |
| A | THR145 |
| A | HOH822 |
| A | HOH989 |
| A | HOH1036 |
| site_id | AC5 |
| Number of Residues | 5 |
| Details | binding site for residue EDO A 705 |
| Chain | Residue |
| A | LYS229 |
| A | ARG482 |
| A | ALA510 |
| A | HOH862 |
| A | HOH947 |
| site_id | AC6 |
| Number of Residues | 7 |
| Details | binding site for residue EDO A 706 |
| Chain | Residue |
| A | ALA371 |
| A | ARG384 |
| A | LEU386 |
| A | HOH835 |
| A | HOH926 |
| A | HOH990 |
| A | HOH1028 |
| site_id | AC7 |
| Number of Residues | 5 |
| Details | binding site for residue EDO A 707 |
| Chain | Residue |
| A | SER212 |
| A | TYR226 |
| A | HOH894 |
| D | HIS255 |
| D | SER467 |
| site_id | AC8 |
| Number of Residues | 5 |
| Details | binding site for residue EDO A 708 |
| Chain | Residue |
| A | GLU250 |
| A | HOH887 |
| D | VAL193 |
| D | TRP206 |
| D | LEU230 |
| site_id | AC9 |
| Number of Residues | 5 |
| Details | binding site for residue EDO A 709 |
| Chain | Residue |
| A | HIS255 |
| A | SER467 |
| A | HOH870 |
| D | SER212 |
| D | TYR226 |
| site_id | AD1 |
| Number of Residues | 5 |
| Details | binding site for residue EDO A 710 |
| Chain | Residue |
| A | ARG71 |
| A | ASN143 |
| A | SER147 |
| A | ILE148 |
| A | PRO68 |
| site_id | AD2 |
| Number of Residues | 5 |
| Details | binding site for residue EDO A 711 |
| Chain | Residue |
| A | ILE248 |
| A | ARG249 |
| A | VAL470 |
| A | ASN474 |
| D | GLU209 |
| site_id | AD3 |
| Number of Residues | 7 |
| Details | binding site for residue EDO A 712 |
| Chain | Residue |
| A | PRO66 |
| A | SER67 |
| A | PRO68 |
| A | ARG71 |
| A | GLY93 |
| A | ARG94 |
| A | SER124 |
| site_id | AD4 |
| Number of Residues | 5 |
| Details | binding site for residue EDO A 713 |
| Chain | Residue |
| A | GLY157 |
| A | PHE190 |
| A | PHE191 |
| A | ARG192 |
| A | HOH917 |
| site_id | AD5 |
| Number of Residues | 5 |
| Details | binding site for residue EDO A 714 |
| Chain | Residue |
| A | TRP289 |
| A | HOH811 |
| A | HOH916 |
| A | HOH1014 |
| A | HOH1073 |
| site_id | AD6 |
| Number of Residues | 5 |
| Details | binding site for residue EDO A 715 |
| Chain | Residue |
| A | PRO46 |
| A | GLU47 |
| A | LYS50 |
| B | LYS58 |
| B | HOH843 |
| site_id | AD7 |
| Number of Residues | 7 |
| Details | binding site for residue EDO A 716 |
| Chain | Residue |
| A | VAL193 |
| A | TRP206 |
| A | LEU230 |
| A | HOH857 |
| A | HOH936 |
| D | GLU250 |
| D | GLY251 |
| site_id | AD8 |
| Number of Residues | 5 |
| Details | binding site for residue EDO A 717 |
| Chain | Residue |
| A | LYS65 |
| A | PRO66 |
| A | GLY93 |
| A | HOH881 |
| A | HOH1107 |
| site_id | AD9 |
| Number of Residues | 18 |
| Details | binding site for residue THG B 601 |
| Chain | Residue |
| B | VAL26 |
| B | VAL27 |
| B | ALA28 |
| B | ASP48 |
| B | MET49 |
| B | PHE52 |
| B | ARG53 |
| B | PRO85 |
| B | PHE88 |
| B | PRO92 |
| B | ARG94 |
| B | ILE154 |
| B | TYR160 |
| B | THR178 |
| B | NAP603 |
| B | HOH714 |
| B | HOH816 |
| B | HOH1060 |
| site_id | AE1 |
| Number of Residues | 14 |
| Details | binding site for residue UMP B 602 |
| Chain | Residue |
| A | ARG383 |
| A | ARG384 |
| B | CYS403 |
| B | HIS404 |
| B | GLN422 |
| B | ARG423 |
| B | SER424 |
| B | ASP426 |
| B | GLY430 |
| B | ASN434 |
| B | HIS464 |
| B | TYR466 |
| B | EDO611 |
| B | HOH978 |
| site_id | AE2 |
| Number of Residues | 27 |
| Details | binding site for residue NAP B 603 |
| Chain | Residue |
| B | VAL27 |
| B | ALA28 |
| B | ILE35 |
| B | GLY36 |
| B | TRP43 |
| B | GLY77 |
| B | ARG78 |
| B | LYS79 |
| B | THR80 |
| B | SER83 |
| B | LEU99 |
| B | SER100 |
| B | SER101 |
| B | THR102 |
| B | GLY130 |
| B | GLY131 |
| B | GLY156 |
| B | GLY157 |
| B | SER158 |
| B | VAL159 |
| B | TYR160 |
| B | THG601 |
| B | HOH714 |
| B | HOH801 |
| B | HOH849 |
| B | HOH855 |
| B | HOH873 |
| site_id | AE3 |
| Number of Residues | 4 |
| Details | binding site for residue EDO B 604 |
| Chain | Residue |
| B | ALA140 |
| B | THR145 |
| B | PHE489 |
| B | HOH828 |
| site_id | AE4 |
| Number of Residues | 7 |
| Details | binding site for residue EDO B 605 |
| Chain | Residue |
| B | TYR176 |
| B | LYS229 |
| B | ILE231 |
| B | ARG482 |
| B | ALA510 |
| B | HOH725 |
| B | HOH765 |
| site_id | AE5 |
| Number of Residues | 7 |
| Details | binding site for residue EDO B 606 |
| Chain | Residue |
| B | ILE248 |
| B | ARG249 |
| B | VAL470 |
| B | ASN474 |
| B | HOH1032 |
| C | GLU209 |
| C | ILE211 |
| site_id | AE6 |
| Number of Residues | 5 |
| Details | binding site for residue EDO B 607 |
| Chain | Residue |
| B | SER467 |
| B | HOH709 |
| B | HOH1036 |
| C | SER212 |
| C | GLU213 |
| site_id | AE7 |
| Number of Residues | 8 |
| Details | binding site for residue EDO B 608 |
| Chain | Residue |
| A | GLY351 |
| A | ASN391 |
| A | SER393 |
| A | HOH1069 |
| B | GLY351 |
| B | ASN391 |
| B | SER393 |
| B | HOH706 |
| site_id | AE8 |
| Number of Residues | 8 |
| Details | binding site for residue EDO B 609 |
| Chain | Residue |
| A | HOH1101 |
| B | ARG271 |
| B | SER412 |
| B | SER417 |
| B | GLU455 |
| B | HOH865 |
| B | HOH871 |
| D | GLU195 |
| site_id | AE9 |
| Number of Residues | 2 |
| Details | binding site for residue EDO B 610 |
| Chain | Residue |
| B | GLY430 |
| B | EDO611 |
| site_id | AF1 |
| Number of Residues | 8 |
| Details | binding site for residue EDO B 611 |
| Chain | Residue |
| B | GLU295 |
| B | PHE299 |
| B | TYR343 |
| B | HIS404 |
| B | ASN434 |
| B | UMP602 |
| B | EDO610 |
| B | HOH734 |
| site_id | AF2 |
| Number of Residues | 6 |
| Details | binding site for residue EDO B 612 |
| Chain | Residue |
| B | GLU250 |
| B | GLY251 |
| B | HOH728 |
| B | HOH898 |
| C | VAL193 |
| C | ARG208 |
| site_id | AF3 |
| Number of Residues | 4 |
| Details | binding site for residue EDO B 613 |
| Chain | Residue |
| B | GLY157 |
| B | PHE190 |
| B | PHE191 |
| B | ARG192 |
| site_id | AF4 |
| Number of Residues | 4 |
| Details | binding site for residue EDO B 614 |
| Chain | Residue |
| B | SER212 |
| B | GLU213 |
| B | HOH891 |
| B | HOH1001 |
| site_id | AF5 |
| Number of Residues | 7 |
| Details | binding site for residue EDO B 615 |
| Chain | Residue |
| B | ALA371 |
| B | ARG384 |
| B | LEU386 |
| B | HOH746 |
| B | HOH869 |
| B | HOH985 |
| B | HOH1044 |
| site_id | AF6 |
| Number of Residues | 16 |
| Details | binding site for residue THG C 601 |
| Chain | Residue |
| C | VAL26 |
| C | VAL27 |
| C | ALA28 |
| C | ASP48 |
| C | MET49 |
| C | PHE52 |
| C | ARG53 |
| C | PHE88 |
| C | LEU91 |
| C | ARG94 |
| C | ILE154 |
| C | TYR160 |
| C | THR178 |
| C | NAP602 |
| C | HOH736 |
| C | HOH787 |
| site_id | AF7 |
| Number of Residues | 26 |
| Details | binding site for residue NAP C 602 |
| Chain | Residue |
| C | VAL27 |
| C | ALA28 |
| C | ILE35 |
| C | GLY36 |
| C | GLY77 |
| C | ARG78 |
| C | LYS79 |
| C | THR80 |
| C | SER83 |
| C | LEU99 |
| C | SER100 |
| C | SER101 |
| C | THR102 |
| C | GLY130 |
| C | GLY131 |
| C | GLY156 |
| C | GLY157 |
| C | SER158 |
| C | VAL159 |
| C | TYR160 |
| C | THG601 |
| C | HOH812 |
| C | HOH818 |
| C | HOH890 |
| C | HOH992 |
| C | HOH1053 |
| site_id | AF8 |
| Number of Residues | 14 |
| Details | binding site for residue UMP C 603 |
| Chain | Residue |
| C | CYS403 |
| C | HIS404 |
| C | GLN422 |
| C | ARG423 |
| C | SER424 |
| C | ASP426 |
| C | GLY430 |
| C | ASN434 |
| C | HIS464 |
| C | TYR466 |
| C | HOH718 |
| C | HOH896 |
| C | HOH921 |
| D | ARG383 |
| site_id | AF9 |
| Number of Residues | 8 |
| Details | binding site for residue EDO C 604 |
| Chain | Residue |
| C | TYR176 |
| C | LYS229 |
| C | ILE231 |
| C | ARG482 |
| C | ALA510 |
| C | EDO611 |
| C | HOH721 |
| C | HOH829 |
| site_id | AG1 |
| Number of Residues | 5 |
| Details | binding site for residue EDO C 605 |
| Chain | Residue |
| B | SER212 |
| B | TYR226 |
| C | HIS255 |
| C | SER467 |
| C | HOH802 |
| site_id | AG2 |
| Number of Residues | 7 |
| Details | binding site for residue EDO C 606 |
| Chain | Residue |
| C | PHE4 |
| C | ARG348 |
| C | HIS349 |
| C | GLU497 |
| C | HOH710 |
| C | HOH761 |
| C | HOH917 |
| site_id | AG3 |
| Number of Residues | 6 |
| Details | binding site for residue EDO C 607 |
| Chain | Residue |
| B | ARG208 |
| B | GLU209 |
| C | ARG249 |
| C | VAL470 |
| C | ASN474 |
| C | HOH1024 |
| site_id | AG4 |
| Number of Residues | 5 |
| Details | binding site for residue EDO C 608 |
| Chain | Residue |
| A | GLU195 |
| C | SER412 |
| C | SER417 |
| D | ASN252 |
| D | HOH1095 |
| site_id | AG5 |
| Number of Residues | 5 |
| Details | binding site for residue EDO C 609 |
| Chain | Residue |
| C | ALA140 |
| C | THR145 |
| C | PHE489 |
| C | HOH770 |
| C | HOH1026 |
| site_id | AG6 |
| Number of Residues | 6 |
| Details | binding site for residue EDO C 610 |
| Chain | Residue |
| A | ARG165 |
| A | PRO166 |
| A | HOH954 |
| C | PRO166 |
| C | PRO167 |
| C | HOH940 |
| site_id | AG7 |
| Number of Residues | 6 |
| Details | binding site for residue EDO C 611 |
| Chain | Residue |
| C | SER24 |
| C | TYR152 |
| C | TYR176 |
| C | EDO604 |
| C | HOH704 |
| C | HOH871 |
| site_id | AG8 |
| Number of Residues | 7 |
| Details | binding site for residue EDO C 612 |
| Chain | Residue |
| C | ALA371 |
| C | ARG384 |
| C | LEU386 |
| C | HOH742 |
| C | HOH759 |
| C | HOH874 |
| C | HOH1032 |
| site_id | AG9 |
| Number of Residues | 2 |
| Details | binding site for residue EDO C 613 |
| Chain | Residue |
| C | THR332 |
| C | HOH701 |
| site_id | AH1 |
| Number of Residues | 3 |
| Details | binding site for residue EDO C 614 |
| Chain | Residue |
| C | TRP289 |
| C | TYR509 |
| C | HOH740 |
| site_id | AH2 |
| Number of Residues | 23 |
| Details | binding site for residue NAP D 701 |
| Chain | Residue |
| D | ALA28 |
| D | ILE35 |
| D | GLY36 |
| D | GLY77 |
| D | ARG78 |
| D | LYS79 |
| D | THR80 |
| D | SER83 |
| D | LEU99 |
| D | SER100 |
| D | SER101 |
| D | THR102 |
| D | GLY130 |
| D | GLY131 |
| D | GLY156 |
| D | GLY157 |
| D | SER158 |
| D | VAL159 |
| D | TYR160 |
| D | THG703 |
| D | HOH813 |
| D | HOH923 |
| D | HOH1101 |
| site_id | AH3 |
| Number of Residues | 15 |
| Details | binding site for residue UMP D 702 |
| Chain | Residue |
| C | ARG383 |
| C | ARG384 |
| D | CYS403 |
| D | HIS404 |
| D | GLN422 |
| D | ARG423 |
| D | SER424 |
| D | ASP426 |
| D | GLY430 |
| D | ASN434 |
| D | HIS464 |
| D | TYR466 |
| D | EDO711 |
| D | HOH802 |
| D | HOH936 |
| site_id | AH4 |
| Number of Residues | 17 |
| Details | binding site for residue THG D 703 |
| Chain | Residue |
| D | VAL26 |
| D | VAL27 |
| D | ALA28 |
| D | ASP48 |
| D | PHE52 |
| D | ARG53 |
| D | PHE88 |
| D | PRO92 |
| D | ARG94 |
| D | ILE154 |
| D | TYR160 |
| D | THR178 |
| D | NAP701 |
| D | HOH813 |
| D | HOH829 |
| D | HOH923 |
| D | HOH930 |
| site_id | AH5 |
| Number of Residues | 7 |
| Details | binding site for residue EDO D 704 |
| Chain | Residue |
| D | TYR176 |
| D | LYS229 |
| D | ILE231 |
| D | ARG482 |
| D | ALA510 |
| D | HOH892 |
| D | HOH963 |
| site_id | AH6 |
| Number of Residues | 8 |
| Details | binding site for residue EDO D 705 |
| Chain | Residue |
| D | ARG348 |
| D | HIS349 |
| D | ASP362 |
| D | GLU497 |
| D | HOH805 |
| D | HOH887 |
| D | HOH922 |
| D | HOH1080 |
| site_id | AH7 |
| Number of Residues | 7 |
| Details | binding site for residue EDO D 706 |
| Chain | Residue |
| A | ARG208 |
| A | GLU209 |
| D | ILE248 |
| D | ARG249 |
| D | VAL470 |
| D | ASN474 |
| D | HOH1018 |
| site_id | AH8 |
| Number of Residues | 3 |
| Details | binding site for residue EDO D 707 |
| Chain | Residue |
| D | ILE316 |
| D | TRP317 |
| D | ASN320 |
| site_id | AH9 |
| Number of Residues | 6 |
| Details | binding site for residue EDO D 708 |
| Chain | Residue |
| D | GLY302 |
| D | THR304 |
| D | HIS357 |
| D | ASP358 |
| D | TYR361 |
| D | HOH995 |
| site_id | AI1 |
| Number of Residues | 8 |
| Details | binding site for residue EDO D 709 |
| Chain | Residue |
| D | ALA371 |
| D | ARG384 |
| D | LEU386 |
| D | HOH872 |
| D | HOH946 |
| D | HOH1003 |
| D | HOH1010 |
| D | HOH1125 |
| site_id | AI2 |
| Number of Residues | 8 |
| Details | binding site for residue EDO D 710 |
| Chain | Residue |
| C | PHE350 |
| C | GLY351 |
| C | ASN391 |
| C | SER393 |
| D | GLY351 |
| D | ASN391 |
| D | SER393 |
| D | HOH832 |
| site_id | AI3 |
| Number of Residues | 2 |
| Details | binding site for residue EDO D 711 |
| Chain | Residue |
| D | GLY430 |
| D | UMP702 |
| site_id | AI4 |
| Number of Residues | 4 |
| Details | binding site for residue EDO D 712 |
| Chain | Residue |
| D | ALA140 |
| D | THR145 |
| D | PHE489 |
| D | HOH912 |
| site_id | AI5 |
| Number of Residues | 7 |
| Details | binding site for residue EDO D 713 |
| Chain | Residue |
| D | ARG286 |
| D | TRP289 |
| D | VAL506 |
| D | TYR509 |
| D | HOH839 |
| D | HOH850 |
| D | HOH1004 |
Functional Information from PROSITE/UniProt
| site_id | PS00075 |
| Number of Residues | 23 |
| Details | DHFR_1 Dihydrofolate reductase (DHFR) domain signature. GIGdgrsIPWnvpe.DmkfFrdlT |
| 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 |
