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 (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 | Comment | Organism |
---|---|---|
additional information | - |
Mus musculus |
additional information | overview about spontaneously occuring mutants and possible mutagenesis studies | Bacteria |
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 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 Maximum [Da] | Comment | Organism |
---|---|---|---|
35000 | - |
bacterial isozyme type II, R factor encoded | Bacteria |
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 | 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 | 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 | 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 | 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 Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
16.5 | - |
7,8-dihydrofolate | - |
Escherichia coli |
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 | 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 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 |