2W3B
HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND A LIPOPHILIC ANTIFOLATE SELECTIVE FOR MYCOBACTERIUM AVIUM DHFR, 6-((2,5- DIETHOXYPHENYL)AMINOMETHYL)-2,4-DIAMINO-5-METHYLPYRIDO(2,3-D) PYRIMIDINE (SRI-8686)
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 | 35 |
| Details | BINDING SITE FOR RESIDUE NDP A 201 |
| Chain | Residue |
| A | VAL8 |
| A | LYS54 |
| A | LYS55 |
| A | THR56 |
| 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 | THR146 |
| A | VG9301 |
| A | FOL401 |
| A | HOH2134 |
| A | HOH2209 |
| A | HOH2234 |
| A | ILE16 |
| A | HOH2300 |
| A | HOH2302 |
| A | HOH2303 |
| A | HOH2304 |
| A | HOH2305 |
| A | HOH2306 |
| A | GLY17 |
| A | LYS18 |
| A | GLY20 |
| A | ASP21 |
| A | LEU22 |
| A | GLY53 |
| site_id | AC2 |
| Number of Residues | 16 |
| Details | BINDING SITE FOR RESIDUE VG9 A 301 |
| Chain | Residue |
| A | ILE7 |
| A | VAL8 |
| A | ALA9 |
| A | ASP21 |
| A | LEU22 |
| A | GLU30 |
| A | PHE31 |
| A | PHE34 |
| A | GLN35 |
| A | SER59 |
| A | PRO61 |
| A | ASN64 |
| A | VAL115 |
| A | TYR121 |
| A | NDP201 |
| A | HOH2305 |
| site_id | AC3 |
| Number of Residues | 19 |
| Details | BINDING SITE FOR RESIDUE FOL A 401 |
| Chain | Residue |
| A | ILE7 |
| A | VAL8 |
| A | ALA9 |
| A | GLU30 |
| A | PHE31 |
| A | ARG32 |
| A | PHE34 |
| A | GLN35 |
| A | ILE60 |
| A | ASN64 |
| A | LEU67 |
| A | ARG70 |
| A | VAL115 |
| A | THR136 |
| A | NDP201 |
| A | HOH2305 |
| A | HOH2308 |
| A | HOH2309 |
| A | HOH2310 |
| site_id | AC4 |
| Number of Residues | 4 |
| Details | BINDING SITE FOR RESIDUE K A 501 |
| Chain | Residue |
| A | SER41 |
| A | VAL43 |
| A | LYS46 |
| A | HOH2111 |
| site_id | AC5 |
| Number of Residues | 30 |
| Details | BINDING SITE FOR RESIDUE NDP B 201 |
| Chain | Residue |
| B | HOH2159 |
| B | HOH2186 |
| B | HOH2264 |
| B | HOH2265 |
| B | HOH2266 |
| B | VAL8 |
| B | ALA9 |
| B | ILE16 |
| B | GLY17 |
| 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 | VAL120 |
| B | TYR121 |
| B | THR146 |
| B | VG9301 |
| B | FOL401 |
| site_id | AC6 |
| Number of Residues | 16 |
| Details | BINDING SITE FOR RESIDUE VG9 B 301 |
| Chain | Residue |
| B | ILE7 |
| B | VAL8 |
| B | ALA9 |
| B | GLU30 |
| B | PHE31 |
| B | PHE34 |
| B | PRO61 |
| B | LEU67 |
| B | ARG70 |
| B | VAL115 |
| B | TYR121 |
| B | NDP201 |
| B | HOH2012 |
| B | HOH2038 |
| B | HOH2264 |
| B | HOH2267 |
| site_id | AC7 |
| Number of Residues | 18 |
| Details | BINDING SITE FOR RESIDUE FOL B 401 |
| Chain | Residue |
| B | ILE7 |
| B | VAL8 |
| B | ALA9 |
| B | GLU30 |
| B | PHE31 |
| B | ARG32 |
| B | PHE34 |
| B | GLN35 |
| B | ILE60 |
| B | ASN64 |
| B | LEU67 |
| B | ARG70 |
| B | VAL115 |
| B | THR136 |
| B | NDP201 |
| B | HOH2047 |
| B | HOH2264 |
| B | HOH2268 |
| site_id | AC8 |
| Number of Residues | 5 |
| Details | BINDING SITE FOR RESIDUE K B 501 |
| Chain | Residue |
| B | SER41 |
| B | VAL43 |
| B | LYS46 |
| B | HOH2078 |
| B | HOH2089 |
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 |
Catalytic Information from CSA
| site_id | CSA1 |
| Number of Residues | 2 |
| Details | Annotated By Reference To The Literature 1dhf |
| Chain | Residue | Details |
| A | LEU22 | |
| A | GLU30 |
| site_id | CSA2 |
| Number of Residues | 2 |
| Details | Annotated By Reference To The Literature 1dhf |
| Chain | Residue | Details |
| B | LEU22 | |
| B | GLU30 |
| 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 |
