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Literature summary for 1.5.1.3 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

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

Crystallization (Commentary)

Crystallization (Comment) Organism
binding to trimethoprim, structure analysis Escherichia coli
comparison of the backbone conformation in crystal structures, detection of mutational insertions Bacteria
comparison of the backbone conformation in crystal structures, detection of mutational insertions vertebrata
no crystallographic data available, but model-based structure analysis Homo sapiens
structure of ternary complex with NADPH and methotrexate Escherichia coli
structure of ternary complex with NADPH and methotrexate Lacticaseibacillus casei
structure of ternary complex with NADPH and phenyltriazine Lacticaseibacillus casei
structure of ternary complex with NADPH and trimethoprim, model development Gallus gallus

Protein Variants

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

Inhibitors

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

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.00047
-
7,8-dihydrofolate
-
Escherichia coli
0.0025 0.0032 NADPH
-
Escherichia coli
0.268
-
NADH
-
Escherichia coli

Molecular Weight [Da]

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

Natural Substrates/ Products (Substrates)

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

Organism

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

Reaction

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

Substrates and Products (Substrate)

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

Subunits

Subunits Comment Organism
dimer
-
Escherichia coli
dimer isozymes type I Bacteria
monomer
-
Gallus gallus
monomer
-
Mus musculus
monomer
-
Escherichia coli
monomer
-
Lacticaseibacillus casei
monomer isozymes type III Bacteria
More overview Bacteria
More overview protozoa
tetramer 4 * 8500-9000, R-plasmid-coded type II reductase Escherichia coli

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
16.5
-
7,8-dihydrofolate
-
Escherichia coli

pH Optimum

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

Cofactor

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

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
additional information
-
Gallus gallus
additional information
-
additional information
-
Mus musculus
additional information
-
additional information
-
Escherichia coli
additional information
-
additional information
-
Homo sapiens
additional information
-
additional information
-
Lacticaseibacillus casei
additional information
-
additional information overview, effect of methotrexate and trimethoprim Bacteria
additional information
-
additional information overview, effect of methotrexate and trimethoprim vertebrata
additional information
-
additional information overview, effect of methotrexate and trimethoprim protozoa
0.000004
-
trimethoprim bacterial chromosomal encoded isozyme type I Bacteria
0.000019
-
trimethoprim bacterial chromosomal encoded isozyme type III Bacteria
0.00009
-
methotrexate bacterial, R factor encoded isozyme type II Bacteria
0.01
-
trimethoprim bacterial, R factor encoded isozymes type I Bacteria