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Literature summary extracted from

  • Freisheim, J.H.; Matthews, D.A.
    The comparative biochemistry of dihydrofolate reductase (1984), Folate Antagonists Ther. Agents (Sirotnak, F. M. , ed. ), 1, 69-131.
No PubMed abstract available

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
1.5.1.3
-
 Escherichia coli
1.5.1.3
-
 Lacticaseibacillus casei
1.5.1.3 comparison of the backbone conformation in crystal structures, detection of mutational insertions Bacteria
1.5.1.3 comparison of the backbone conformation in crystal structures, detection of mutational insertions vertebrata

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.5.1.3 2,4,6-Trinitrobenzenesulfonic acid
-
 Enterococcus faecium
1.5.1.3 2,4-Diamino-5-adamantylpyrimidine weak inhibition Gallus gallus
1.5.1.3 2,4-Diamino-5-adamantylpyrimidine weak inhibition vertebrata
1.5.1.3 2,4-Diamino-5-benzylpyrimidines
-
 Gallus gallus
1.5.1.3 2,4-Diamino-5-phenyl-s-triazines
-
 Gallus gallus
1.5.1.3 2,4-Pentanedione
-
 Lacticaseibacillus casei
1.5.1.3 4,6-Diamino-1,2-dihydro-2,2-dimethyl-1-(phenylalkylphenyl)-s-triazines bearing a terminal sulfonyl fluoride Gallus gallus
1.5.1.3 Dansyl chloride
-
 Lacticaseibacillus casei
1.5.1.3 diethyldicarbonate
-
 Enterococcus faecium
1.5.1.3 diethyldicarbonate
-
 Escherichia coli
1.5.1.3 diethyldicarbonate
-
 Lacticaseibacillus casei
1.5.1.3 diethyldicarbonate
-
 Mus musculus
1.5.1.3 methotrexate dihydrofolate antagonist drug Bacteria
1.5.1.3 methotrexate
-
 Bos taurus
1.5.1.3 methotrexate
-
 Crithidia fasciculata
1.5.1.3 methotrexate dihydrofolate antagonist drug Escherichia coli
1.5.1.3 methotrexate also ornithine, lysine and dansyl analogs of methotrexate Gallus gallus
1.5.1.3 methotrexate dihydrofolate antagonist drug Homo sapiens
1.5.1.3 methotrexate
-
 Lacticaseibacillus casei
1.5.1.3 methotrexate dihydrofolate antagonist drug Mammalia
1.5.1.3 methotrexate dihydrofolate antagonist drug Mus musculus
1.5.1.3 methotrexate
-
 Sus scrofa
1.5.1.3 methotrexate
-
 Tequatrovirus T4
1.5.1.3 additional information stereochemistry of inhibitor binding Bacteria
1.5.1.3 additional information
-
 Bos taurus
1.5.1.3 additional information
-
 Crithidia fasciculata
1.5.1.3 additional information
-
 Enterococcus faecium
1.5.1.3 additional information stereochemistry of inhibitor binding Escherichia coli
1.5.1.3 additional information stereochemistry of inhibitor binding Gallus gallus
1.5.1.3 additional information stereochemistry of inhibitor binding Lacticaseibacillus casei
1.5.1.3 additional information
-
 Mus musculus
1.5.1.3 additional information stereochemistry of inhibitor binding protozoa
1.5.1.3 additional information
-
 Sus scrofa
1.5.1.3 additional information stereochemistry of inhibitor binding vertebrata
1.5.1.3 N-bromosuccinimide
-
 Lacticaseibacillus casei
1.5.1.3 organic mercurials animal enzyme: activated, bacterial enzyme: unaffected or inhibited Enterococcus faecium
1.5.1.3 organic mercurials animal enzyme: activated, bacterial enzyme: unaffected or inhibited Escherichia coli
1.5.1.3 Phenylglyoxal total inactivation Lacticaseibacillus casei
1.5.1.3 trimethoprim folate antagonist drug Bacteria
1.5.1.3 trimethoprim
-
 Bos taurus
1.5.1.3 trimethoprim
-
 Crithidia fasciculata
1.5.1.3 trimethoprim
-
 Escherichia coli
1.5.1.3 trimethoprim
-
 Gallus gallus
1.5.1.3 trimethoprim
-
 Homo sapiens
1.5.1.3 trimethoprim
-
 Lacticaseibacillus casei
1.5.1.3 trimethoprim folate antagonist drug Mammalia
1.5.1.3 trimethoprim folate antagonist drug Mus musculus
1.5.1.3 trimethoprim
-
 Sus scrofa
1.5.1.3 trimethoprim
-
 vertebrata

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.5.1.3 additional information
-
 additional information
-
 Mammalia
1.5.1.3 additional information
-
 additional information
-
 Tequatrovirus T4
1.5.1.3 additional information
-
 additional information overview Gallus gallus
1.5.1.3 additional information
-
 additional information overview Bacteria
1.5.1.3 additional information
-
 additional information overview Mus musculus
1.5.1.3 additional information
-
 additional information overview Escherichia coli
1.5.1.3 additional information
-
 additional information overview Homo sapiens
1.5.1.3 additional information
-
 additional information overview Sus scrofa
1.5.1.3 additional information
-
 additional information overview Bos taurus
1.5.1.3 additional information
-
 additional information overview Crithidia fasciculata
1.5.1.3 additional information
-
 additional information overview Lacticaseibacillus casei
1.5.1.3 additional information
-
 additional information overview Enterococcus faecium
1.5.1.3 additional information
-
 additional information overview vertebrata
1.5.1.3 additional information
-
 additional information overview protozoa
1.5.1.3 additional information
-
 additional information Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes Gallus gallus
1.5.1.3 additional information
-
 additional information Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes Bacteria
1.5.1.3 additional information
-
 additional information Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes Mus musculus
1.5.1.3 additional information
-
 additional information Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes Escherichia coli
1.5.1.3 additional information
-
 additional information Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes Homo sapiens
1.5.1.3 additional information
-
 additional information Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes Sus scrofa
1.5.1.3 additional information
-
 additional information Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes Bos taurus
1.5.1.3 additional information
-
 additional information Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes Crithidia fasciculata
1.5.1.3 additional information
-
 additional information Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes Lacticaseibacillus casei
1.5.1.3 additional information
-
 additional information Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes Enterococcus faecium
1.5.1.3 additional information
-
 additional information Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes vertebrata
1.5.1.3 additional information
-
 additional information Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes protozoa

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.5.1.3 organic mercurials
-
 Mammalia
1.5.1.3 organic mercurials
-
 Lacticaseibacillus casei
1.5.1.3 organic mercurials animal enzyme: activated, bacterial enzyme: unaffected or inhibited Gallus gallus
1.5.1.3 organic mercurials animal enzyme: activated, bacterial enzyme: unaffected or inhibited Mus musculus
1.5.1.3 organic mercurials animal enzyme: activated, bacterial enzyme: unaffected or inhibited Homo sapiens
1.5.1.3 organic mercurials animal enzyme: activated, bacterial enzyme: unaffected or inhibited Sus scrofa
1.5.1.3 organic mercurials animal enzyme: activated, bacterial enzyme: unaffected or inhibited Bos taurus

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
1.5.1.3 18250
-
 MB 1428, amino acid sequence Escherichia coli
1.5.1.3 18300
-
 amino acid sequence Lacticaseibacillus casei
1.5.1.3 19600
-
 isoenzyme II, amino acid sequence Enterococcus faecium
1.5.1.3 21450
-
 amino acid sequence Sus scrofa
1.5.1.3 21450
-
 amino acid sequence Bos taurus
1.5.1.3 21460
-
 methotrexate resistant L1210(R) cells, amino acid sequence Mus musculus
1.5.1.3 21650
-
 amino acid sequence Gallus gallus
1.5.1.3 56700
-
 2 * 56700, bifunctional enzyme: thymidylate synthase-dihydrofolate reductase, SDS-PAGE Crithidia fasciculata
1.5.1.3 107000
-
 bifunctional enzyme: thymidylate synthase-dihydrofolate reductase Crithidia fasciculata

Organism

EC Number Organism UniProt Comment Textmining
1.5.1.3 Bacteria
-
 overview
-
1.5.1.3 Bos taurus
-
-
-
1.5.1.3 Crithidia fasciculata
-
 bifunctional enzyme: dihydrofolate reductase-thymidylate synthase EC 2.1.1.45
-
1.5.1.3 Enterococcus faecium
-
-
-
1.5.1.3 Escherichia coli
-
 various strains
-
1.5.1.3 Gallus gallus
-
-
-
1.5.1.3 Homo sapiens
-
 methotrexate-resistant WIL-2 lymphoblastoid cells
-
1.5.1.3 Lacticaseibacillus casei
-
-
-
1.5.1.3 Mammalia
-
 cultured mammalian cells, overview
-
1.5.1.3 Mus musculus
-
 L1210 lymphoma cells, amethopterin-resistant
-
1.5.1.3 protozoa
-
 overview
-
1.5.1.3 Streptococcus pneumoniae
-
 methotrexate-resistant form
-
1.5.1.3 Sus scrofa
-
-
-
1.5.1.3 Tequatrovirus T4
-
-
-
1.5.1.3 vertebrata
-
 overview
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.5.1.3
-
 Escherichia coli
1.5.1.3
-
 Tequatrovirus T4

Reaction

EC Number Reaction Comment Organism Reaction ID
1.5.1.3 5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+ catalytic mechanism Bacteria
a
1.5.1.3 5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+ catalytic mechanism Escherichia coli
a
1.5.1.3 5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+ catalytic mechanism Lacticaseibacillus casei
a
1.5.1.3 5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+ catalytic mechanism Enterococcus faecium
a
1.5.1.3 5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+ catalytic mechanism vertebrata
a
1.5.1.3 5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+ catalytic mechanism protozoa
a

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.5.1.3 liver
-
 Gallus gallus
-
1.5.1.3 liver
-
 Mus musculus
-
1.5.1.3 liver
-
 Sus scrofa
-
1.5.1.3 liver
-
 Bos taurus
-

Specific Activity [micromol/min/mg]

EC Number Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
1.5.1.3 11
-
 methotrexate resistant cells, L1210 (R), 25°C Mus musculus
1.5.1.3 12
-
 30°C Lacticaseibacillus casei
1.5.1.3 14
-
 chicken liver, 28°C Gallus gallus
1.5.1.3 15
-
 human WIL2 (M4) cells, 22°C Homo sapiens
1.5.1.3 26
-
 bovine liver, 28°C Bos taurus
1.5.1.3 27
-
 methotrexate resistant cells, sarcoma 180 (AT/3000), 37°C Mammalia
1.5.1.3 36
-
 methotrexate resistant, 23°C Escherichia coli
1.5.1.3 36
-
 liver, 30°C Sus scrofa
1.5.1.3 45
-
-
 Escherichia coli
1.5.1.3 45
-
 methotrexate resistant cells, isoenzyme II, 37°C Enterococcus faecium
1.5.1.3 55
-
 trimethoprim resistant, 30°C Escherichia coli
1.5.1.3 60
-
 human KB cells, 37°C Homo sapiens
1.5.1.3 300
-
 isoenzyme I Enterococcus faecium
1.5.1.3 300
-
 25°C Enterococcus faecium
1.5.1.3 300
-
 methotrexate resistant cells Enterococcus faecium

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.5.1.3 7,8-dihydrofolate + NADPH
-
 Gallus gallus 5,6,7,8-tetrahydrofolate + NADP+
-
 ?
1.5.1.3 7,8-dihydrofolate + NADPH
-
 Mammalia 5,6,7,8-tetrahydrofolate + NADP+
-
 ?
1.5.1.3 7,8-dihydrofolate + NADPH
-
 Bacteria 5,6,7,8-tetrahydrofolate + NADP+
-
 ?
1.5.1.3 7,8-dihydrofolate + NADPH
-
 Mus musculus 5,6,7,8-tetrahydrofolate + NADP+
-
 ?
1.5.1.3 7,8-dihydrofolate + NADPH
-
 Escherichia coli 5,6,7,8-tetrahydrofolate + NADP+
-
 ?
1.5.1.3 7,8-dihydrofolate + NADPH
-
 Homo sapiens 5,6,7,8-tetrahydrofolate + NADP+
-
 ?
1.5.1.3 7,8-dihydrofolate + NADPH
-
 Sus scrofa 5,6,7,8-tetrahydrofolate + NADP+
-
 ?
1.5.1.3 7,8-dihydrofolate + NADPH
-
 Bos taurus 5,6,7,8-tetrahydrofolate + NADP+
-
 ?
1.5.1.3 7,8-dihydrofolate + NADPH
-
 Crithidia fasciculata 5,6,7,8-tetrahydrofolate + NADP+
-
 ?
1.5.1.3 7,8-dihydrofolate + NADPH
-
 Lacticaseibacillus casei 5,6,7,8-tetrahydrofolate + NADP+
-
 ?
1.5.1.3 7,8-dihydrofolate + NADPH
-
 Enterococcus faecium 5,6,7,8-tetrahydrofolate + NADP+
-
 ?
1.5.1.3 7,8-dihydrofolate + NADPH
-
 vertebrata 5,6,7,8-tetrahydrofolate + NADP+
-
 ?
1.5.1.3 7,8-dihydrofolate + NADPH
-
 protozoa 5,6,7,8-tetrahydrofolate + NADP+
-
 ?

Subunits

EC Number Subunits Comment Organism
1.5.1.3 dimer
-
 Bacteria
1.5.1.3 dimer
-
 Escherichia coli
1.5.1.3 dimer 2 * 56700, bifunctional enzyme: thymidylate synthase-dihydrofolate reductase, SDS-PAGE Crithidia fasciculata
1.5.1.3 monomer
-
 Bacteria
1.5.1.3 monomer
-
 Tequatrovirus T4
1.5.1.3 monomer 1 * 21650, amino acid sequence Gallus gallus
1.5.1.3 monomer 1 * 21450, amino acid sequence Sus scrofa
1.5.1.3 monomer 1 * 21450, amino acid sequence Bos taurus
1.5.1.3 monomer 1 * 21460, methotrexate resistant L1210 (R) cells, amino acid sequence Mus musculus
1.5.1.3 monomer 1 * 18250, MB 1428, amino acid sequence Escherichia coli
1.5.1.3 monomer 1 * 19600, isoenzyme II, amino acid sequence Enterococcus faecium
1.5.1.3 monomer 1 * 18300, amino acid sequence Lacticaseibacillus casei
1.5.1.3 More
-
 Crithidia fasciculata
1.5.1.3 More overview Bacteria
1.5.1.3 More overview Tequatrovirus T4
1.5.1.3 More overview protozoa
1.5.1.3 tetramer 4 * 8500-9000, R-plasmid-coded type II reductase Escherichia coli

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.5.1.3 3.67
-
 NADPH pH 6.5 Lacticaseibacillus casei

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.5.1.3 4
-
 methotrexate resistant cells L1210 (R), sarcoma 180 (AT/300), 2 optima: pH 4 and pH 7.5 Mammalia
1.5.1.3 4
-
 methotrexate resistant cells L1210 (R), sarcoma 180 (AT/300), 2 optima: pH 4 and pH 7.5 Mus musculus
1.5.1.3 4
-
 7,8-dihydrofolate + NADPH, 2 optima: pH 4 and pH 7.4 Gallus gallus
1.5.1.3 4
-
 human WIL 2 cell line, 2 optima: pH 4 and pH 7.3-8.3 Homo sapiens
1.5.1.3 4.8 5
-
 Bos taurus
1.5.1.3 5
-
 2 optima: pH 5 and pH 7.6 Sus scrofa
1.5.1.3 5.8
-
 7,8-dihydrofolate, isoenzyme II, methotrexate resistant cells Enterococcus faecium
1.5.1.3 6.5
-
-
 Escherichia coli
1.5.1.3 6.5
-
-
 Lacticaseibacillus casei
1.5.1.3 6.5
-
 isoenzyme I, methotrexate resistant cells Enterococcus faecium
1.5.1.3 6.8
-
-
 Crithidia fasciculata
1.5.1.3 6.8
-
 MB 1328 Escherichia coli
1.5.1.3 7.2 8.2 KB cells, 2 optima: below pH 5.0 and pH 7.2-8.2 Homo sapiens
1.5.1.3 7.3 8.3 WIL2 (M4) cells, 2 optima: pH 4 and pH 7.3-8.3 Homo sapiens
1.5.1.3 7.4
-
 7,8-dihydrofolate + NADPH, 2 optima: pH 4.0 and pH 7.4 Gallus gallus
1.5.1.3 7.5
-
-
 Homo sapiens
1.5.1.3 7.5
-
 methotrexate resistant cells, L1210(R), sarcoma 180 (AT/30000), 2 optima: pH 4.0 and pH 7.5 Mammalia
1.5.1.3 7.5
-
 methotrexate resistant cells, L1210(R), sarcoma 180 (AT/30000), 2 optima: pH 4.0 and pH 7.5 Mus musculus
1.5.1.3 7.6
-
-
 Escherichia coli
1.5.1.3 7.6
-
-
 Sus scrofa

Cofactor

EC Number Cofactor Comment Organism Structure
1.5.1.3 NADPH
-
 Gallus gallus
1.5.1.3 NADPH
-
 Mammalia
1.5.1.3 NADPH
-
 Mus musculus
1.5.1.3 NADPH
-
 Escherichia coli
1.5.1.3 NADPH
-
 Homo sapiens
1.5.1.3 NADPH
-
 Sus scrofa
1.5.1.3 NADPH
-
 Bos taurus
1.5.1.3 NADPH
-
 Crithidia fasciculata
1.5.1.3 NADPH
-
 Streptococcus pneumoniae
1.5.1.3 NADPH
-
 Lacticaseibacillus casei
1.5.1.3 NADPH
-
 Enterococcus faecium
1.5.1.3 NADPH
-
 Tequatrovirus T4
1.5.1.3 NADPH interaction study Bacteria
1.5.1.3 NADPH interaction study vertebrata

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
1.5.1.3 additional information
-
 additional information
-
 Gallus gallus
1.5.1.3 additional information
-
 additional information
-
 Mus musculus
1.5.1.3 additional information
-
 additional information
-
 Escherichia coli
1.5.1.3 additional information
-
 additional information
-
 Homo sapiens
1.5.1.3 additional information
-
 additional information
-
 Lacticaseibacillus casei
1.5.1.3 additional information
-
 additional information overview, effect of methotrexate and trimethoprim Bacteria
1.5.1.3 additional information
-
 additional information overview, effect of methotrexate and trimethoprim vertebrata
1.5.1.3 additional information
-
 additional information overview, effect of methotrexate and trimethoprim protozoa