Dihydrofolate reductase

Function

Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.

Classification

Family (Pfam)

PF00186 DHFR_1

InterPro

DHFR, DHFR-like_dom_sf, DHFR_CS, DHFR_dom

Functional cluster

Nucleotide & Shikimate Kinases

Experimental structures · PDB · 161

• 1DDR X-ray 2.45A
• 1DDS X-ray 2.20A
• 1DHI X-ray 1.90A
• 1DHJ X-ray 1.80A
• 1DRA X-ray 1.90A
• 1DRB X-ray 1.96A
• 1DRE X-ray 2.60A
• 1DRH X-ray 2.30A
• 1DYH X-ray 1.90A
• 1DYI X-ray 1.90A
• 1DYJ X-ray 1.85A
• 1JOL X-ray 1.96A
• … and 149 more

A predicted model is available from AlphaFold.

Gene Ontology · 17

• GO:0005829 cytosol
• GO:0004146 dihydrofolate reductase activity
• GO:0051871 dihydrofolic acid binding
• GO:0005542 folic acid binding
• GO:0051870 methotrexate binding
• GO:0050661 NADP binding
• GO:0070401 NADP+ binding
• GO:0070402 NADPH binding
• GO:0009257 10-formyltetrahydrofolate biosynthetic process
• GO:0046452 dihydrofolate metabolic process
• GO:0046656 folic acid biosynthetic process
• GO:0046655 folic acid metabolic process
• GO:0006730 one-carbon metabolic process
• GO:0046677 response to antibiotic
• GO:0031427 response to methotrexate
• GO:0009410 response to xenobiotic stimulus
• GO:0046654 tetrahydrofolate biosynthetic process

Drugs targeting this protein · 5

• TRIMETHOPRIM HYDROCHLORIDE inhibitor
• ICLAPRIM inhibitor
• TRIMETHOPRIM SULFATE inhibitor
• TRIMETHOPRIM inhibitor
• CO-TRIMOXAZOLE inhibitor

Related proteins · sequence + function similarity

• Dihydrofolate reductase 1.00
• Dihydrofolate reductase 0.99
• Dihydrofolate reductase 0.98
• Dihydrofolate reductase 0.82
• Dihydrofolate reductase 0.82
• Dihydrofolate reductase type 3 0.77
• Dihydrofolate reductase type 5 0.76
• Dihydrofolate reductase 0.75
• Dihydrofolate reductase type 15 0.72
• Dihydrofolate reductase 0.72
• Dihydrofolate reductase type 1 0.71
• Dihydrofolate reductase 0.71

Co-cited proteins · studied together in the literature

• Dihydrofolate reductase 1 shared papers
• Glutathione-regulated potassium-efflux system protein KefC 1 shared papers

Literature · 19 cited papers

• X-ray structure of the ternary MTX.NADPH complex of the anthrax dihydrofolate reductase: a pharmacophore for dual-site inhibitor design. J. Struct. Biol. · 2009
• Neutron diffraction studies of Escherichia coli dihydrofolate reductase complexed with methotrexate. Proc. Natl. Acad. Sci. U.S.A. · 2006
• A 2.13 A structure of E. coli dihydrofolate reductase bound to a novel competitive inhibitor reveals a new binding surface involving the M20 loop region. J. Med. Chem. · 2006
• Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol. Syst. Biol. · 2006
• Evolutional design of a hyperactive cysteine- and methionine-free mutant of Escherichia coli dihydrofolate reductase. J. Biol. Chem. · 2006
• Escherichia coli proteome analysis using the gene-protein database. Electrophoresis · 1997
• The complete genome sequence of Escherichia coli K-12. Science · 1997
• Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: crystallographic evidence. Biochemistry · 1997
• Crystal structures of Escherichia coli dihydrofolate reductase complexed with 5-formyltetrahydrofolate (folinic acid) in two space groups: evidence for enolization of pteridine O4. Biochemistry · 1996
• Isomorphous crystal structures of Escherichia coli dihydrofolate reductase complexed with folate, 5-deazafolate, and 5,10-dideazatetrahydrofolate: mechanistic implications. Biochemistry · 1995
• Effect of a single amino acid substitution on Escherichia coli dihydrofolate reductase catalysis and ligand binding. J. Biol. Chem. · 1981
• Crystal structures of Escherichia coli and Lactobacillus casei dihydrofolate reductase refined at 1.7-A resolution. II. Environment of bound NADPH and implications for catalysis. J. Biol. Chem. · 1982
• … and 7 more in the literature graph