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DrugBank target: P00374

DrugBank target: P00374 (DYR_HUMAN)     

Example drug-target structure: 2w3a

( There are 63 structures corresponding to this UniProt sequence in the PDB. Click the orange, plus icon above for a list. )

Dihydrofolate reductase

Function

Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1. {ECO:0000269|PubMed:12096917, ECO:0000269|PubMed:21876188}..

Enzyme

1.5.1.3   [EC->PDB]   [IntEnz]   [ExPASy]   [KEGG]  

Catalytic activity

5,6,7,8-tetrahydrofolate + NADP(+) = 7,8- dihydrofolate + NADPH. {ECO:0000255|PROSITE-ProRule:PRU00660, ECO:0000269|PubMed:12096917, ECO:0000269|PubMed:15039552, ECO:0000269|PubMed:17569517, ECO:0000269|PubMed:19196009, ECO:0000269|PubMed:19478082, ECO:0000269|PubMed:21876184, ECO:0000269|PubMed:9719595}.

Disease(s)

Megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD) [MIM:613839]: An inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms. {ECO:0000269|PubMed:21310276, ECO:0000269|PubMed:21310277}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Schematic diagram of Pfam domains in target sequence plus wiring diagram of PDB structure containing drug molecule

2w3a

Key:    PfamA domain  Secondary structure  Bound drug molecule

Sequence length: 186 a.a.

Approved drugs / nutraceuticals targeting this protein

The DrugBank database identifies 7 drugs and and 1 nutraceutical for this target protein:

 

Generic name: DB00205 pyrimethamine
CP6
Formula: C12H13Cln4
Structure: There are 9 PDB structures containing this molecule although none are bound to the above target protein.
Generic name: DB00642 pemetrexed
LYA
Formula: C20H21N5O6
Structure: There are 7 PDB structures containing this molecule although none are bound to the above target protein.
Generic name: DB00440 trimethoprim
TOP
Formula: C14H18N4O3
Structure: There are 18 PDB structures containing this molecule of which 3 are bound to the above target protein.
Generic name: DB00157 nadh
NAI
Formula: C21H29N7O14P2
Structure: There are 164 PDB structures containing this molecule although none are bound to the above target protein.
Generic name: DB01157 trimetrexate
TMQ
Formula: C19H23N5O3
Structure: There are 5 PDB structures containing this molecule although none are bound to the above target protein.
 
Generic name: DB06813 pralatrexate
Formula: C23H23N7O5
Structure: There are no structures of this molecule in the PDB.
 
Generic name: DB01131 proguanil
Formula: C11H16Cln5
Structure: There are no structures of this molecule in the PDB.
Generic name: DB00563 methotrexate
MT1
Formula: C20H22N8O5
Structure: There are 2 PDB structures containing this molecule although none are bound to the above target protein.

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