4DFR
CRYSTAL STRUCTURES OF ESCHERICHIA COLI AND LACTOBACILLUS CASEI DIHYDROFOLATE REDUCTASE REFINED AT 1.7 ANGSTROMS RESOLUTION. I. GENERAL FEATURES AND BINDING OF METHOTREXATE
Replaces: 2DFRFunctional Information from GO Data
| Chain | GOid | namespace | contents |
| A | 0004146 | molecular_function | dihydrofolate reductase activity |
| A | 0005515 | molecular_function | protein binding |
| A | 0005542 | molecular_function | folic acid binding |
| A | 0005829 | cellular_component | cytosol |
| A | 0006545 | biological_process | glycine biosynthetic process |
| A | 0006730 | biological_process | one-carbon metabolic process |
| A | 0009410 | biological_process | response to xenobiotic stimulus |
| A | 0016491 | molecular_function | oxidoreductase activity |
| A | 0031427 | biological_process | response to methotrexate |
| A | 0046452 | biological_process | dihydrofolate metabolic process |
| A | 0046654 | biological_process | tetrahydrofolate biosynthetic process |
| A | 0046655 | biological_process | folic acid metabolic process |
| A | 0046677 | biological_process | response to antibiotic |
| A | 0050661 | molecular_function | NADP binding |
| A | 0051870 | molecular_function | methotrexate binding |
| A | 0051871 | molecular_function | dihydrofolic acid binding |
| A | 0070401 | molecular_function | NADP+ binding |
| A | 0070402 | molecular_function | NADPH binding |
| B | 0004146 | molecular_function | dihydrofolate reductase activity |
| B | 0005515 | molecular_function | protein binding |
| B | 0005542 | molecular_function | folic acid binding |
| B | 0005829 | cellular_component | cytosol |
| B | 0006545 | biological_process | glycine biosynthetic process |
| B | 0006730 | biological_process | one-carbon metabolic process |
| B | 0009410 | biological_process | response to xenobiotic stimulus |
| B | 0016491 | molecular_function | oxidoreductase activity |
| B | 0031427 | biological_process | response to methotrexate |
| B | 0046452 | biological_process | dihydrofolate metabolic process |
| B | 0046654 | biological_process | tetrahydrofolate biosynthetic process |
| B | 0046655 | biological_process | folic acid metabolic process |
| B | 0046677 | biological_process | response to antibiotic |
| B | 0050661 | molecular_function | NADP binding |
| B | 0051870 | molecular_function | methotrexate binding |
| B | 0051871 | molecular_function | dihydrofolic acid binding |
| B | 0070401 | molecular_function | NADP+ binding |
| B | 0070402 | molecular_function | NADPH binding |
Functional Information from PDB Data
| site_id | AAB |
| Number of Residues | 5 |
| Details | RESIDUES INTERACTING WITH THE P-AMINO BENZOYL OF THE METHOTREXATE INHIBITOR |
| Chain | Residue |
| A | LEU28 |
| A | PHE31 |
| A | ILE50 |
| A | ARG52 |
| A | LEU54 |
| site_id | AC1 |
| Number of Residues | 6 |
| Details | BINDING SITE FOR RESIDUE CL A 160 |
| Chain | Residue |
| A | GLY43 |
| A | HIS45 |
| A | THR46 |
| A | GLY96 |
| A | HOH230 |
| A | HOH374 |
| site_id | AC2 |
| Number of Residues | 4 |
| Details | BINDING SITE FOR RESIDUE CL B 160 |
| Chain | Residue |
| B | GLY43 |
| B | THR46 |
| B | GLY96 |
| B | HOH285 |
| site_id | AC3 |
| Number of Residues | 6 |
| Details | BINDING SITE FOR RESIDUE CA B 161 |
| Chain | Residue |
| A | HOH250 |
| B | SER135 |
| B | HOH205 |
| B | HOH206 |
| B | HOH207 |
| B | HOH221 |
| site_id | AC4 |
| Number of Residues | 14 |
| Details | BINDING SITE FOR RESIDUE MTX A 161 |
| Chain | Residue |
| A | ILE5 |
| A | ALA6 |
| A | ASP27 |
| A | PHE31 |
| A | LYS32 |
| A | ARG52 |
| A | ARG57 |
| A | ILE94 |
| A | TYR100 |
| A | THR113 |
| A | HOH263 |
| A | HOH296 |
| A | HOH323 |
| A | HOH328 |
| site_id | AC5 |
| Number of Residues | 17 |
| Details | BINDING SITE FOR RESIDUE MTX B 162 |
| Chain | Residue |
| B | ILE5 |
| B | ALA6 |
| B | ALA7 |
| B | ASP27 |
| B | LEU28 |
| B | PHE31 |
| B | LYS32 |
| B | ILE50 |
| B | ARG52 |
| B | LEU54 |
| B | ARG57 |
| B | ILE94 |
| B | TYR100 |
| B | THR113 |
| B | HOH202 |
| B | HOH242 |
| B | HOH260 |
| site_id | AGL |
| Number of Residues | 5 |
| Details | RESIDUES INTERACTING WITH THE GLUTAMATE OF THE METHOTREXATE INHIBITOR |
| Chain | Residue |
| A | LEU28 |
| A | PHE31 |
| A | LYS32 |
| A | LEU54 |
| A | ARG57 |
| site_id | ANM |
| Number of Residues | 1 |
| Details | RESIDUES INTERACTING WITH THE N(10) METHYL OF THE METHOTREXATE INHIBITOR |
| Chain | Residue |
| A | SER49 |
| site_id | APT |
| Number of Residues | 12 |
| Details | RESIDUES INTERACTING WITH THE PTERIDINE OF THE METHOTREXATE INHIBITOR. INCLUDE WATER MOLECULES WHICH ARE BOUND EITHER TO INVARIANT SIDE CHAINS OR TO STRUCTURALLY INVARIANT MAIN CHAIN SEGMENTS. |
| Chain | Residue |
| A | ILE5 |
| A | HOH163 |
| A | HOH165 |
| A | HOH172 |
| A | ALA6 |
| A | ALA7 |
| A | TRP22 |
| A | ASP27 |
| A | LEU28 |
| A | PHE31 |
| A | ILE94 |
| A | THR113 |
| site_id | BAB |
| Number of Residues | 5 |
| Details | RESIDUES INTERACTING WITH THE P-AMINO BENZOYL OF THE METHOTREXATE INHIBITOR |
| Chain | Residue |
| B | LEU28 |
| B | PHE31 |
| B | ILE50 |
| B | ARG52 |
| B | LEU54 |
| site_id | BGL |
| Number of Residues | 5 |
| Details | RESIDUES INTERACTING WITH THE GLUTAMATE OF THE METHOTREXATE INHIBITOR |
| Chain | Residue |
| B | LEU28 |
| B | PHE31 |
| B | LYS32 |
| B | LEU54 |
| B | ARG57 |
| site_id | BNM |
| Number of Residues | 1 |
| Details | RESIDUES INTERACTING WITH THE N(10) METHYL OF THE METHOTREXATE INHIBITOR |
| Chain | Residue |
| B | SER49 |
| site_id | BPT |
| Number of Residues | 12 |
| Details | RESIDUES INTERACTING WITH THE PTERIDINE OF THE METHOTREXATE INHIBITOR. INCLUDE WATER MOLECULES WHICH ARE BOUND EITHER TO INVARIANT SIDE CHAINS OR TO STRUCTURALLY INVARIANT MAIN CHAIN SEGMENTS. |
| Chain | Residue |
| B | ILE5 |
| B | ALA6 |
| B | ALA7 |
| B | TRP22 |
| B | ASP27 |
| B | LEU28 |
| B | PHE31 |
| B | ILE94 |
| B | THR113 |
| B | HOH170 |
| B | HOH171 |
| B | HOH202 |
Functional Information from PROSITE/UniProt
| site_id | PS00075 |
| Number of Residues | 23 |
| Details | DHFR_1 Dihydrofolate reductase (DHFR) domain signature. VIGmenaMPWnlpa.DlawFkrnT |
| Chain | Residue | Details |
| A | VAL13-THR35 |
Functional Information from SwissProt/UniProt
| site_id | SWS_FT_FI1 |
| Number of Residues | 10 |
| Details | BINDING: BINDING => ECO:0000305|PubMed:9012674 |
| Chain | Residue | Details |
| A | ILE5 | |
| B | THR113 | |
| A | ASP27 | |
| A | ARG52 | |
| A | ARG57 | |
| A | THR113 | |
| B | ILE5 | |
| B | ASP27 | |
| B | ARG52 | |
| B | ARG57 |
| site_id | SWS_FT_FI2 |
| Number of Residues | 12 |
| Details | BINDING: BINDING => ECO:0000269|PubMed:19374017 |
| Chain | Residue | Details |
| A | ALA7 | |
| B | SER63 | |
| B | LYS76 | |
| B | GLY95 | |
| A | VAL13 | |
| A | HIS45 | |
| A | SER63 | |
| A | LYS76 | |
| A | GLY95 | |
| B | ALA7 | |
| B | VAL13 | |
| B | HIS45 |
