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Literature summary extracted from

  • Kraut, J.; Matthews, D.A.
    Dihydrofolate reductase (1987), Biol. Macromol. and Assem. (Junak, F. , McPherson, eds. ), 3, 1-71.
No PubMed abstract available

Activating Compound

EC Number Activating Compound Comment Organism Structure
1.5.1.3 Cl-
-
Homo sapiens
1.5.1.3 Cl- a few bacterial and vertebrate enzymes are activated at concentrations of 0.3-0.5 M Bacteria
1.5.1.3 Cl- a few bacterial and vertebrate enzymes are activated at concentrations of 0.3-0.5 M vertebrata
1.5.1.3 Urea
-
Homo sapiens
1.5.1.3 Urea
-
Lacticaseibacillus casei
1.5.1.3 Urea increase in Km and kcat values for 7,8-dihydrofolate and NADPH Gallus gallus

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
1.5.1.3 binding to trimethoprim, structure analysis Escherichia coli
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
1.5.1.3 no crystallographic data available, but model-based structure analysis Homo sapiens
1.5.1.3 structure of ternary complex with NADPH and methotrexate Escherichia coli
1.5.1.3 structure of ternary complex with NADPH and methotrexate Lacticaseibacillus casei
1.5.1.3 structure of ternary complex with NADPH and phenyltriazine Lacticaseibacillus casei
1.5.1.3 structure of ternary complex with NADPH and trimethoprim, model development Gallus gallus

Protein Variants

EC Number Protein Variants Comment Organism
1.5.1.3 additional information
-
Mus musculus
1.5.1.3 additional information overview about spontaneously occuring mutants and possible mutagenesis studies Bacteria

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.5.1.3 2,4-diamino-5-methyl-butylpyrido[2,3-d]pyrimidine
-
Bacteria
1.5.1.3 2,4-Dimamino-6-butylpyrido[2,3-d]pyrimidine
-
Bacteria
1.5.1.3 methotrexate
-
Bacteria
1.5.1.3 methotrexate
-
Escherichia coli
1.5.1.3 methotrexate
-
Gallus gallus
1.5.1.3 methotrexate
-
Homo sapiens
1.5.1.3 methotrexate
-
Lacticaseibacillus casei
1.5.1.3 methotrexate
-
Mus musculus
1.5.1.3 additional information overview; stereochemistry of inhibitor binding Bacteria
1.5.1.3 additional information overview; stereochemistry of inhibitor binding Escherichia coli
1.5.1.3 additional information overview; stereochemistry of inhibitor binding Gallus gallus
1.5.1.3 additional information overview; stereochemistry of inhibitor binding Lacticaseibacillus casei
1.5.1.3 additional information overview Mus musculus
1.5.1.3 additional information overview Pigeon
1.5.1.3 additional information stereochemistry of inhibitor binding protozoa
1.5.1.3 additional information stereochemistry of inhibitor binding vertebrata
1.5.1.3 pyrimethamine i.e. 2,4-diamino-5-p-chlorophenyl-6-ethylpyridine Bacteria
1.5.1.3 pyrimethamine
-
Gallus gallus
1.5.1.3 pyrimethamine
-
Homo sapiens
1.5.1.3 pyrimethamine
-
Mus musculus
1.5.1.3 trimethoprim
-
Bacteria
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
-
Mus musculus
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 0.00047
-
7,8-dihydrofolate
-
Escherichia coli
1.5.1.3 0.0025 0.0032 NADPH
-
Escherichia coli
1.5.1.3 0.268
-
NADH
-
Escherichia coli

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
1.5.1.3 35000
-
bacterial isozyme type II, R factor encoded Bacteria

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.5.1.3 7,8-dihydrofolate + NADPH Homo sapiens
-
5,6,7,8-tetrahydrofolate + NADP+
-
?
1.5.1.3 7,8-dihydrofolate + NADPH Gallus gallus maintainance of adequate levels of fully reduced folate in metabolism of proliferating cells 5,6,7,8-tetrahydrofolate + NADP+
-
?
1.5.1.3 7,8-dihydrofolate + NADPH Bacteria maintainance of adequate levels of fully reduced folate in metabolism of proliferating cells 5,6,7,8-tetrahydrofolate + NADP+
-
?
1.5.1.3 7,8-dihydrofolate + NADPH Bacteria directly correlated with thymidylate synthesis 5,6,7,8-tetrahydrofolate + NADP+
-
?

Organism

EC Number Organism UniProt Comment Textmining
1.5.1.3 Bacteria
-
overview
-
1.5.1.3 Escherichia coli
-
-
-
1.5.1.3 Gallus gallus
-
-
-
1.5.1.3 Homo sapiens
-
methotrexate-resistant WIL-2 lymphoblastoid cells
-
1.5.1.3 Klebsiella aerogenes
-
R-plasmid encoded, trimethoprim-resistant
-
1.5.1.3 Lacticaseibacillus casei
-
-
-
1.5.1.3 Mus musculus
-
L1210 lymphoma cells, amethopterin-resistant
-
1.5.1.3 Pigeon
-
-
-
1.5.1.3 protozoa
-
-
-
1.5.1.3 vertebrata
-
overview
-

Reaction

EC Number Reaction Comment Organism Reaction ID
1.5.1.3 5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+ rapid equilibrium random mechanism Bacteria
1.5.1.3 5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+ catalytic mechanism Bacteria
1.5.1.3 5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+ catalytic mechanism Escherichia coli
1.5.1.3 5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+ catalytic mechanism Lacticaseibacillus casei
1.5.1.3 5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+ catalytic mechanism vertebrata
1.5.1.3 5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+ catalytic mechanism protozoa
1.5.1.3 5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+ substrate and cofactor binding mechanism Bacteria

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.5.1.3 7,8-dihydrofolate + NADH + H+
-
Escherichia coli 5,6,7,8-tetrahydrofolate + NAD+
-
r
1.5.1.3 7,8-dihydrofolate + NADPH
-
Gallus gallus 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
-
Homo sapiens 5,6,7,8-tetrahydrofolate + NADP+
-
?
1.5.1.3 7,8-dihydrofolate + NADPH
-
Pigeon 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+
-
?
1.5.1.3 7,8-dihydrofolate + NADPH equilibrium strongly favors tetrahydrofolate production Bacteria 5,6,7,8-tetrahydrofolate + NADP+
-
?
1.5.1.3 7,8-dihydrofolate + NADPH equilibrium strongly favors tetrahydrofolate production Bacteria 5,6,7,8-tetrahydrofolate + NADP+
-
r
1.5.1.3 7,8-dihydrofolate + NADPH equilibrium strongly favors tetrahydrofolate production Escherichia coli 5,6,7,8-tetrahydrofolate + NADP+
-
?
1.5.1.3 7,8-dihydrofolate + NADPH equilibrium strongly favors tetrahydrofolate production Escherichia coli 5,6,7,8-tetrahydrofolate + NADP+
-
r
1.5.1.3 7,8-dihydrofolate + NADPH equilibrium strongly favors tetrahydrofolate production Lacticaseibacillus casei 5,6,7,8-tetrahydrofolate + NADP+
-
?
1.5.1.3 7,8-dihydrofolate + NADPH equilibrium strongly favors tetrahydrofolate production Lacticaseibacillus casei 5,6,7,8-tetrahydrofolate + NADP+
-
r
1.5.1.3 7,8-dihydrofolate + NADPH maintainance of adequate levels of fully reduced folate in metabolism of proliferating cells Gallus gallus 5,6,7,8-tetrahydrofolate + NADP+
-
?
1.5.1.3 7,8-dihydrofolate + NADPH maintainance of adequate levels of fully reduced folate in metabolism of proliferating cells Bacteria 5,6,7,8-tetrahydrofolate + NADP+
-
?
1.5.1.3 7,8-dihydrofolate + NADPH directly correlated with thymidylate synthesis Bacteria 5,6,7,8-tetrahydrofolate + NADP+
-
?

Subunits

EC Number Subunits Comment Organism
1.5.1.3 dimer
-
Escherichia coli
1.5.1.3 dimer isozymes type I Bacteria
1.5.1.3 monomer
-
Gallus gallus
1.5.1.3 monomer
-
Mus musculus
1.5.1.3 monomer
-
Escherichia coli
1.5.1.3 monomer
-
Lacticaseibacillus casei
1.5.1.3 monomer isozymes type III Bacteria
1.5.1.3 More overview Bacteria
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 16.5
-
7,8-dihydrofolate
-
Escherichia coli

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.5.1.3 4.5
-
folic acid reduction Bacteria
1.5.1.3 4.5
-
folic acid reduction Escherichia coli
1.5.1.3 7
-
-
Escherichia coli
1.5.1.3 7
-
7,8-dihydrofolate reduction Bacteria

Cofactor

EC Number Cofactor Comment Organism Structure
1.5.1.3 NADPH
-
Bacteria
1.5.1.3 NADPH
-
Mus musculus
1.5.1.3 NADPH
-
Homo sapiens
1.5.1.3 NADPH
-
Pigeon
1.5.1.3 NADPH
-
vertebrata
1.5.1.3 NADPH cofactor-enzyme interaction study from x-ray structure, structural and topological comparison with dehydrogenases Gallus gallus
1.5.1.3 NADPH cofactor-enzyme interaction study from x-ray structure, structural and topological comparison with dehydrogenases Escherichia coli
1.5.1.3 NADPH cofactor-enzyme interaction study from x-ray structure, structural and topological comparison with dehydrogenases Lacticaseibacillus casei

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
1.5.1.3 0.000004
-
trimethoprim bacterial chromosomal encoded isozyme type I Bacteria
1.5.1.3 0.000019
-
trimethoprim bacterial chromosomal encoded isozyme type III Bacteria
1.5.1.3 0.00009
-
methotrexate bacterial, R factor encoded isozyme type II Bacteria
1.5.1.3 0.01
-
trimethoprim bacterial, R factor encoded isozymes type I Bacteria