6VCJ
Crystal structure of hsDHFR in complex with NADP+, DAP, and R-naproxen
Functional Information from GO Data
| Chain | GOid | namespace | contents |
| A | 0000900 | molecular_function | mRNA regulatory element binding translation repressor activity |
| A | 0003723 | molecular_function | RNA binding |
| A | 0003729 | molecular_function | mRNA binding |
| A | 0004146 | molecular_function | dihydrofolate reductase activity |
| A | 0005515 | molecular_function | protein binding |
| A | 0005542 | molecular_function | folic acid binding |
| A | 0005737 | cellular_component | cytoplasm |
| A | 0005739 | cellular_component | mitochondrion |
| A | 0005829 | cellular_component | cytosol |
| A | 0006729 | biological_process | tetrahydrobiopterin biosynthetic process |
| A | 0006730 | biological_process | one-carbon metabolic process |
| A | 0008144 | molecular_function | obsolete drug binding |
| A | 0016491 | molecular_function | oxidoreductase activity |
| A | 0017148 | biological_process | negative regulation of translation |
| A | 0031103 | biological_process | axon regeneration |
| A | 0031427 | biological_process | response to methotrexate |
| A | 0046452 | biological_process | dihydrofolate metabolic process |
| A | 0046653 | biological_process | tetrahydrofolate metabolic process |
| A | 0046654 | biological_process | tetrahydrofolate biosynthetic process |
| A | 0046655 | biological_process | folic acid metabolic process |
| A | 0050661 | molecular_function | NADP binding |
| A | 0070402 | molecular_function | NADPH binding |
| A | 1990825 | molecular_function | sequence-specific mRNA binding |
| A | 2000121 | biological_process | regulation of removal of superoxide radicals |
| B | 0000900 | molecular_function | mRNA regulatory element binding translation repressor activity |
| B | 0003723 | molecular_function | RNA binding |
| B | 0003729 | molecular_function | mRNA binding |
| B | 0004146 | molecular_function | dihydrofolate reductase activity |
| B | 0005515 | molecular_function | protein binding |
| B | 0005542 | molecular_function | folic acid binding |
| B | 0005737 | cellular_component | cytoplasm |
| B | 0005739 | cellular_component | mitochondrion |
| B | 0005829 | cellular_component | cytosol |
| B | 0006729 | biological_process | tetrahydrobiopterin biosynthetic process |
| B | 0006730 | biological_process | one-carbon metabolic process |
| B | 0008144 | molecular_function | obsolete drug binding |
| B | 0016491 | molecular_function | oxidoreductase activity |
| B | 0017148 | biological_process | negative regulation of translation |
| B | 0031103 | biological_process | axon regeneration |
| B | 0031427 | biological_process | response to methotrexate |
| B | 0046452 | biological_process | dihydrofolate metabolic process |
| B | 0046653 | biological_process | tetrahydrofolate metabolic process |
| B | 0046654 | biological_process | tetrahydrofolate biosynthetic process |
| B | 0046655 | biological_process | folic acid metabolic process |
| B | 0050661 | molecular_function | NADP binding |
| B | 0070402 | molecular_function | NADPH binding |
| B | 1990825 | molecular_function | sequence-specific mRNA binding |
| B | 2000121 | biological_process | regulation of removal of superoxide radicals |
| C | 0000900 | molecular_function | mRNA regulatory element binding translation repressor activity |
| C | 0003723 | molecular_function | RNA binding |
| C | 0003729 | molecular_function | mRNA binding |
| C | 0004146 | molecular_function | dihydrofolate reductase activity |
| C | 0005515 | molecular_function | protein binding |
| C | 0005542 | molecular_function | folic acid binding |
| C | 0005737 | cellular_component | cytoplasm |
| C | 0005739 | cellular_component | mitochondrion |
| C | 0005829 | cellular_component | cytosol |
| C | 0006729 | biological_process | tetrahydrobiopterin biosynthetic process |
| C | 0006730 | biological_process | one-carbon metabolic process |
| C | 0008144 | molecular_function | obsolete drug binding |
| C | 0016491 | molecular_function | oxidoreductase activity |
| C | 0017148 | biological_process | negative regulation of translation |
| C | 0031103 | biological_process | axon regeneration |
| C | 0031427 | biological_process | response to methotrexate |
| C | 0046452 | biological_process | dihydrofolate metabolic process |
| C | 0046653 | biological_process | tetrahydrofolate metabolic process |
| C | 0046654 | biological_process | tetrahydrofolate biosynthetic process |
| C | 0046655 | biological_process | folic acid metabolic process |
| C | 0050661 | molecular_function | NADP binding |
| C | 0070402 | molecular_function | NADPH binding |
| C | 1990825 | molecular_function | sequence-specific mRNA binding |
| C | 2000121 | biological_process | regulation of removal of superoxide radicals |
| D | 0000900 | molecular_function | mRNA regulatory element binding translation repressor activity |
| D | 0003723 | molecular_function | RNA binding |
| D | 0003729 | molecular_function | mRNA binding |
| D | 0004146 | molecular_function | dihydrofolate reductase activity |
| D | 0005515 | molecular_function | protein binding |
| D | 0005542 | molecular_function | folic acid binding |
| D | 0005737 | cellular_component | cytoplasm |
| D | 0005739 | cellular_component | mitochondrion |
| D | 0005829 | cellular_component | cytosol |
| D | 0006729 | biological_process | tetrahydrobiopterin biosynthetic process |
| D | 0006730 | biological_process | one-carbon metabolic process |
| D | 0008144 | molecular_function | obsolete drug binding |
| D | 0016491 | molecular_function | oxidoreductase activity |
| D | 0017148 | biological_process | negative regulation of translation |
| D | 0031103 | biological_process | axon regeneration |
| D | 0031427 | biological_process | response to methotrexate |
| D | 0046452 | biological_process | dihydrofolate metabolic process |
| D | 0046653 | biological_process | tetrahydrofolate metabolic process |
| D | 0046654 | biological_process | tetrahydrofolate biosynthetic process |
| D | 0046655 | biological_process | folic acid metabolic process |
| D | 0050661 | molecular_function | NADP binding |
| D | 0070402 | molecular_function | NADPH binding |
| D | 1990825 | molecular_function | sequence-specific mRNA binding |
| D | 2000121 | biological_process | regulation of removal of superoxide radicals |
Functional Information from PDB Data
| site_id | AC1 |
| Number of Residues | 9 |
| Details | binding site for residue LG3 A 201 |
| Chain | Residue |
| A | ILE7 |
| A | VAL8 |
| A | ALA9 |
| A | GLU30 |
| A | PHE34 |
| A | TYR121 |
| A | NAP203 |
| A | FOL204 |
| A | HOH312 |
| site_id | AC2 |
| Number of Residues | 7 |
| Details | binding site for residue NPX A 202 |
| Chain | Residue |
| A | PHE34 |
| A | GLN35 |
| A | SER59 |
| A | ASN64 |
| A | ARG70 |
| A | NAP203 |
| A | FOL204 |
| site_id | AC3 |
| Number of Residues | 30 |
| Details | binding site for residue NAP A 203 |
| Chain | Residue |
| A | VAL8 |
| A | ALA9 |
| A | ILE16 |
| A | GLY17 |
| A | GLY20 |
| A | ASP21 |
| A | GLY53 |
| A | LYS54 |
| A | LYS55 |
| A | THR56 |
| A | SER59 |
| A | LEU75 |
| A | SER76 |
| A | ARG77 |
| A | GLU78 |
| A | ARG91 |
| A | SER92 |
| A | VAL115 |
| A | GLY117 |
| A | SER118 |
| A | SER119 |
| A | VAL120 |
| A | TYR121 |
| A | THR146 |
| A | LG3201 |
| A | NPX202 |
| A | FOL204 |
| A | HOH302 |
| A | HOH303 |
| A | HOH310 |
| site_id | AC4 |
| Number of Residues | 15 |
| Details | binding site for residue FOL A 204 |
| Chain | Residue |
| A | ILE7 |
| A | VAL8 |
| A | LEU22 |
| A | GLU30 |
| A | PHE31 |
| A | PHE34 |
| A | GLN35 |
| A | ASN64 |
| A | LEU67 |
| A | ARG70 |
| A | VAL115 |
| A | LG3201 |
| A | NPX202 |
| A | NAP203 |
| A | HOH312 |
| site_id | AC5 |
| Number of Residues | 8 |
| Details | binding site for residue LG3 B 201 |
| Chain | Residue |
| B | ILE7 |
| B | VAL8 |
| B | GLU30 |
| B | PHE34 |
| B | THR136 |
| B | NPX202 |
| B | NAP203 |
| B | FOL204 |
| site_id | AC6 |
| Number of Residues | 8 |
| Details | binding site for residue NPX B 202 |
| Chain | Residue |
| B | PHE31 |
| B | PHE34 |
| B | SER59 |
| B | ASN64 |
| B | ARG70 |
| B | LG3201 |
| B | NAP203 |
| B | FOL204 |
| site_id | AC7 |
| Number of Residues | 33 |
| Details | binding site for residue NAP B 203 |
| Chain | Residue |
| B | THR146 |
| B | LG3201 |
| B | NPX202 |
| B | FOL204 |
| B | HOH303 |
| B | HOH305 |
| B | HOH306 |
| B | HOH307 |
| B | HOH310 |
| B | HOH311 |
| D | ASN13 |
| B | VAL8 |
| B | ALA9 |
| B | ILE16 |
| B | GLY17 |
| B | GLY20 |
| B | ASP21 |
| B | LEU22 |
| B | GLY53 |
| B | LYS54 |
| B | LYS55 |
| B | THR56 |
| B | SER59 |
| B | LEU75 |
| B | SER76 |
| B | ARG77 |
| B | GLU78 |
| B | ARG91 |
| B | VAL115 |
| B | GLY117 |
| B | SER118 |
| B | SER119 |
| B | TYR121 |
| site_id | AC8 |
| Number of Residues | 15 |
| Details | binding site for residue FOL B 204 |
| Chain | Residue |
| B | ILE7 |
| B | VAL8 |
| B | ALA9 |
| B | GLU30 |
| B | PHE31 |
| B | PHE34 |
| B | GLN35 |
| B | ASN64 |
| B | ARG70 |
| B | VAL115 |
| B | THR136 |
| B | LG3201 |
| B | NPX202 |
| B | NAP203 |
| B | HOH312 |
| site_id | AC9 |
| Number of Residues | 9 |
| Details | binding site for residue LG3 C 201 |
| Chain | Residue |
| C | ILE7 |
| C | VAL8 |
| C | GLU30 |
| C | PHE34 |
| C | TYR121 |
| C | THR136 |
| C | NPX202 |
| C | NAP203 |
| C | FOL204 |
| site_id | AD1 |
| Number of Residues | 9 |
| Details | binding site for residue NPX C 202 |
| Chain | Residue |
| C | PHE34 |
| C | GLN35 |
| C | SER59 |
| C | ILE60 |
| C | PRO61 |
| C | ASN64 |
| C | ARG70 |
| C | LG3201 |
| C | FOL204 |
| site_id | AD2 |
| Number of Residues | 26 |
| Details | binding site for residue NAP C 203 |
| Chain | Residue |
| C | VAL8 |
| C | ALA9 |
| C | ILE16 |
| C | GLY20 |
| C | ASP21 |
| C | GLY53 |
| C | LYS54 |
| C | LYS55 |
| C | THR56 |
| C | SER59 |
| C | LEU75 |
| C | SER76 |
| C | ARG77 |
| C | GLU78 |
| C | ARG91 |
| C | VAL115 |
| C | GLY117 |
| C | SER118 |
| C | SER119 |
| C | TYR121 |
| C | THR146 |
| C | LG3201 |
| C | FOL204 |
| C | HOH312 |
| C | HOH314 |
| C | HOH316 |
| site_id | AD3 |
| Number of Residues | 15 |
| Details | binding site for residue FOL C 204 |
| Chain | Residue |
| C | ILE7 |
| C | VAL8 |
| C | ALA9 |
| C | GLU30 |
| C | PHE34 |
| C | GLN35 |
| C | ASN64 |
| C | LEU67 |
| C | LYS68 |
| C | ARG70 |
| C | VAL115 |
| C | THR136 |
| C | LG3201 |
| C | NPX202 |
| C | NAP203 |
| site_id | AD4 |
| Number of Residues | 7 |
| Details | binding site for residue LG3 D 201 |
| Chain | Residue |
| D | ILE7 |
| D | VAL8 |
| D | GLU30 |
| D | PHE34 |
| D | NPX202 |
| D | NAP203 |
| D | FOL204 |
| site_id | AD5 |
| Number of Residues | 10 |
| Details | binding site for residue NPX D 202 |
| Chain | Residue |
| D | PHE31 |
| D | PHE34 |
| D | GLN35 |
| D | SER59 |
| D | ASN64 |
| D | LEU67 |
| D | ARG70 |
| D | LG3201 |
| D | NAP203 |
| D | FOL204 |
| site_id | AD6 |
| Number of Residues | 28 |
| Details | binding site for residue NAP D 203 |
| Chain | Residue |
| D | VAL8 |
| D | ALA9 |
| D | ILE16 |
| D | GLY17 |
| D | GLY20 |
| D | ASP21 |
| D | LEU22 |
| D | GLY53 |
| D | LYS54 |
| D | LYS55 |
| D | THR56 |
| D | SER59 |
| D | LEU75 |
| D | SER76 |
| D | ARG77 |
| D | GLU78 |
| D | ARG91 |
| D | VAL115 |
| D | GLY117 |
| D | SER118 |
| D | SER119 |
| D | VAL120 |
| D | TYR121 |
| D | THR146 |
| D | LG3201 |
| D | NPX202 |
| D | FOL204 |
| D | HOH309 |
| site_id | AD7 |
| Number of Residues | 16 |
| Details | binding site for residue FOL D 204 |
| Chain | Residue |
| D | ILE7 |
| D | VAL8 |
| D | ALA9 |
| D | LEU22 |
| D | GLU30 |
| D | PHE31 |
| D | PHE34 |
| D | GLN35 |
| D | ASN64 |
| D | LEU67 |
| D | ARG70 |
| D | VAL115 |
| D | THR136 |
| D | LG3201 |
| D | NPX202 |
| D | NAP203 |
Functional Information from PROSITE/UniProt
| site_id | PS00075 |
| Number of Residues | 24 |
| Details | DHFR_1 Dihydrofolate reductase (DHFR) domain signature. GIGkngdLPWpplrnEfryFqrmT |
| Chain | Residue | Details |
| A | GLY15-THR38 |
Functional Information from SwissProt/UniProt
| site_id | SWS_FT_FI1 |
| Number of Residues | 20 |
| Details | BINDING: BINDING => ECO:0000269|PubMed:15039552, ECO:0000269|PubMed:16222560, ECO:0000269|PubMed:19478082 |
| Chain | Residue | Details |
| A | ALA9 | |
| B | GLY116 | |
| C | ALA9 | |
| C | GLY15 | |
| C | LYS54 | |
| C | SER76 | |
| C | GLY116 | |
| D | ALA9 | |
| D | GLY15 | |
| D | LYS54 | |
| D | SER76 | |
| A | GLY15 | |
| D | GLY116 | |
| A | LYS54 | |
| A | SER76 | |
| A | GLY116 | |
| B | ALA9 | |
| B | GLY15 | |
| B | LYS54 | |
| B | SER76 |
| site_id | SWS_FT_FI2 |
| Number of Residues | 12 |
| Details | BINDING: BINDING => ECO:0000305|PubMed:2248959 |
| Chain | Residue | Details |
| A | GLU30 | |
| D | GLU30 | |
| D | ASN64 | |
| D | ARG70 | |
| A | ASN64 | |
| A | ARG70 | |
| B | GLU30 | |
| B | ASN64 | |
| B | ARG70 | |
| C | GLU30 | |
| C | ASN64 | |
| C | ARG70 |
Catalytic Information from CSA
| site_id | MCSA1 |
| Number of Residues | 2 |
| Details | M-CSA 490 |
| Chain | Residue | Details |
| A | LEU22 | electrostatic stabiliser |
| A | GLU30 | electrostatic stabiliser |
| site_id | MCSA2 |
| Number of Residues | 2 |
| Details | M-CSA 490 |
| Chain | Residue | Details |
| B | LEU22 | electrostatic stabiliser |
| B | GLU30 | electrostatic stabiliser |
| site_id | MCSA3 |
| Number of Residues | 2 |
| Details | M-CSA 490 |
| Chain | Residue | Details |
| C | LEU22 | electrostatic stabiliser |
| C | GLU30 | electrostatic stabiliser |
| site_id | MCSA4 |
| Number of Residues | 2 |
| Details | M-CSA 490 |
| Chain | Residue | Details |
| D | LEU22 | electrostatic stabiliser |
| D | GLU30 | electrostatic stabiliser |
