4KAK
Crystal structure of human dihydrofolate reductase complexed with NADPH and 6-ethyl-5-[(3S)-3-[3-methoxy-5-(pyridine-4-yl)phenyl]but-1-yn-1-yl]pyrimidine-2,4-diamine (UCP1006)
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 | 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 | 0051000 | biological_process | positive regulation of nitric-oxide synthase activity |
| 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 | 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 | 0051000 | biological_process | positive regulation of nitric-oxide synthase activity |
| B | 0070402 | molecular_function | NADPH binding |
| B | 1990825 | molecular_function | sequence-specific mRNA binding |
| B | 2000121 | biological_process | regulation of removal of superoxide radicals |
Functional Information from PDB Data
| site_id | AC1 |
| Number of Residues | 29 |
| Details | BINDING SITE FOR RESIDUE NDP A 201 |
| Chain | Residue |
| A | VAL8 |
| A | LYS55 |
| A | THR56 |
| A | SER59 |
| A | LEU75 |
| A | SER76 |
| A | ARG77 |
| A | GLU78 |
| A | ARG91 |
| A | VAL115 |
| A | GLY117 |
| A | ALA9 |
| A | SER118 |
| A | SER119 |
| A | VAL120 |
| A | TYR121 |
| A | GLU123 |
| A | THR146 |
| A | 06U202 |
| A | HOH326 |
| A | HOH372 |
| A | HOH416 |
| A | ILE16 |
| A | GLY17 |
| A | GLY20 |
| A | ASP21 |
| A | LEU22 |
| A | GLY53 |
| A | LYS54 |
| site_id | AC2 |
| Number of Residues | 16 |
| Details | BINDING SITE FOR RESIDUE 06U A 202 |
| Chain | Residue |
| A | ILE7 |
| A | VAL8 |
| A | ALA9 |
| A | ASP21 |
| A | GLU30 |
| A | PHE31 |
| A | PHE34 |
| A | SER59 |
| A | PRO61 |
| A | ASN64 |
| A | LEU67 |
| A | VAL115 |
| A | TYR121 |
| A | THR136 |
| A | NDP201 |
| A | HOH454 |
| site_id | AC3 |
| Number of Residues | 5 |
| Details | BINDING SITE FOR RESIDUE EOH A 203 |
| Chain | Residue |
| A | ASP21 |
| A | LEU22 |
| A | TRP24 |
| A | HOH380 |
| B | GLU161 |
| site_id | AC4 |
| Number of Residues | 2 |
| Details | BINDING SITE FOR RESIDUE EOH A 204 |
| Chain | Residue |
| A | GLY2 |
| B | GLU171 |
| site_id | AC5 |
| Number of Residues | 3 |
| Details | BINDING SITE FOR RESIDUE EOH A 205 |
| Chain | Residue |
| A | GLN47 |
| A | LYS68 |
| A | GLY69 |
| site_id | AC6 |
| Number of Residues | 5 |
| Details | BINDING SITE FOR RESIDUE CA A 206 |
| Chain | Residue |
| A | SER3 |
| A | ASN5 |
| A | LYS132 |
| A | HOH381 |
| A | HOH438 |
| site_id | AC7 |
| Number of Residues | 30 |
| Details | BINDING SITE FOR RESIDUE NDP B 201 |
| Chain | Residue |
| B | VAL8 |
| B | ALA9 |
| B | ILE16 |
| B | GLY17 |
| B | GLY20 |
| B | ASP21 |
| B | TRP24 |
| 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 | VAL120 |
| B | GLU123 |
| B | THR146 |
| B | 06U202 |
| B | HOH309 |
| B | HOH320 |
| B | HOH395 |
| B | HOH409 |
| B | HOH414 |
| site_id | AC8 |
| Number of Residues | 13 |
| Details | BINDING SITE FOR RESIDUE 06U B 202 |
| Chain | Residue |
| B | ASN64 |
| B | VAL115 |
| B | THR136 |
| B | NDP201 |
| B | ILE7 |
| B | VAL8 |
| B | ALA9 |
| B | ASP21 |
| B | GLU30 |
| B | PHE31 |
| B | PHE34 |
| B | SER59 |
| B | PRO61 |
| site_id | AC9 |
| Number of Residues | 3 |
| Details | BINDING SITE FOR RESIDUE EOH B 203 |
| Chain | Residue |
| A | LYS157 |
| B | PRO61 |
| B | GLU62 |
| site_id | BC1 |
| Number of Residues | 2 |
| Details | BINDING SITE FOR RESIDUE EOH B 204 |
| Chain | Residue |
| A | GLU62 |
| B | LYS157 |
| site_id | BC2 |
| Number of Residues | 4 |
| Details | BINDING SITE FOR RESIDUE CA B 205 |
| Chain | Residue |
| B | ARG32 |
| B | HOH390 |
| B | HOH428 |
| B | HOH438 |
| site_id | BC3 |
| Number of Residues | 6 |
| Details | BINDING SITE FOR RESIDUE CA B 206 |
| Chain | Residue |
| B | VAL10 |
| B | GLN12 |
| B | ARG137 |
| B | ILE138 |
| B | HOH317 |
| B | HOH380 |
| site_id | BC4 |
| Number of Residues | 6 |
| Details | BINDING SITE FOR RESIDUE CA B 207 |
| Chain | Residue |
| A | PRO25 |
| A | LYS173 |
| A | HOH383 |
| B | TYR162 |
| B | GLU183 |
| B | HOH388 |
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 | 10 |
| Details | BINDING: BINDING => ECO:0000269|PubMed:15039552, ECO:0000269|PubMed:16222560, ECO:0000269|PubMed:19478082 |
| Chain | Residue | Details |
| A | ALA9 | |
| B | GLY116 | |
| A | GLY15 | |
| A | LYS54 | |
| A | SER76 | |
| A | GLY116 | |
| B | ALA9 | |
| B | GLY15 | |
| B | LYS54 | |
| B | SER76 |
| site_id | SWS_FT_FI2 |
| Number of Residues | 6 |
| Details | BINDING: BINDING => ECO:0000305|PubMed:2248959 |
| Chain | Residue | Details |
| A | GLU30 | |
| A | ASN64 | |
| A | ARG70 | |
| B | GLU30 | |
| B | ASN64 | |
| B | ARG70 |
