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Literature summary for 1.5.1.3 extracted from
- The comparative biochemistry of dihydrofolate reductase (1984), Folate Antagonists Ther. Agents (Sirotnak, F. M. , ed. ), 1, 69-131.
No PubMed abstract available
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
- |
Escherichia coli |
- |
Lacticaseibacillus casei |
| 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 |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 2,4,6-Trinitrobenzenesulfonic acid | - |
Enterococcus faecium |  |
| 2,4-Diamino-5-adamantylpyrimidine | weak inhibition | Gallus gallus | |
| 2,4-Diamino-5-adamantylpyrimidine | weak inhibition | vertebrata | |
| 2,4-Diamino-5-benzylpyrimidines | - |
Gallus gallus | |
| 2,4-Diamino-5-phenyl-s-triazines | - |
Gallus gallus | |
| 2,4-Pentanedione | - |
Lacticaseibacillus casei | |
| 4,6-Diamino-1,2-dihydro-2,2-dimethyl-1-(phenylalkylphenyl)-s-triazines | bearing a terminal sulfonyl fluoride | Gallus gallus | |
| Dansyl chloride | - |
Lacticaseibacillus casei | |
| diethyldicarbonate | - |
Enterococcus faecium | |
| diethyldicarbonate | - |
Escherichia coli | |
| diethyldicarbonate | - |
Lacticaseibacillus casei | |
| diethyldicarbonate | - |
Mus musculus | |
| methotrexate | dihydrofolate antagonist drug | Bacteria | |
| methotrexate | - |
Bos taurus | |
| methotrexate | - |
Crithidia fasciculata | |
| methotrexate | dihydrofolate antagonist drug | Escherichia coli | |
| methotrexate | also ornithine, lysine and dansyl analogs of methotrexate | Gallus gallus | |
| methotrexate | dihydrofolate antagonist drug | Homo sapiens | |
| methotrexate | - |
Lacticaseibacillus casei | |
| methotrexate | dihydrofolate antagonist drug | Mammalia | |
| methotrexate | dihydrofolate antagonist drug | Mus musculus | |
| methotrexate | - |
Sus scrofa | |
| methotrexate | - |
Tequatrovirus T4 | |
| additional information | stereochemistry of inhibitor binding | Bacteria | |
| additional information | - |
Bos taurus | |
| additional information | - |
Crithidia fasciculata | |
| additional information | - |
Enterococcus faecium | |
| additional information | stereochemistry of inhibitor binding | Escherichia coli | |
| additional information | stereochemistry of inhibitor binding | Gallus gallus | |
| additional information | stereochemistry of inhibitor binding | Lacticaseibacillus casei | |
| additional information | - |
Mus musculus | |
| additional information | stereochemistry of inhibitor binding | protozoa | |
| additional information | - |
Sus scrofa | |
| additional information | stereochemistry of inhibitor binding | vertebrata | |
| N-bromosuccinimide | - |
Lacticaseibacillus casei | |
| organic mercurials | animal enzyme: activated, bacterial enzyme: unaffected or inhibited | Enterococcus faecium | |
| organic mercurials | animal enzyme: activated, bacterial enzyme: unaffected or inhibited | Escherichia coli | |
| Phenylglyoxal | total inactivation | Lacticaseibacillus casei | |
| trimethoprim | folate antagonist drug | Bacteria | |
| trimethoprim | - |
Bos taurus | |
| trimethoprim | - |
Crithidia fasciculata | |
| trimethoprim | - |
Escherichia coli | |
| trimethoprim | - |
Gallus gallus | |
| trimethoprim | - |
Homo sapiens | |
| trimethoprim | - |
Lacticaseibacillus casei | |
| trimethoprim | folate antagonist drug | Mammalia | |
| trimethoprim | folate antagonist drug | Mus musculus | |
| trimethoprim | - |
Sus scrofa | |
| trimethoprim | - |
vertebrata | |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | - |
Mammalia | |
| additional information | - |
additional information | - |
Tequatrovirus T4 | |
| additional information | - |
additional information | overview | Gallus gallus | |
| additional information | - |
additional information | overview | Bacteria | |
| additional information | - |
additional information | overview | Mus musculus | |
| additional information | - |
additional information | overview | Escherichia coli | |
| additional information | - |
additional information | overview | Homo sapiens | |
| additional information | - |
additional information | overview | Sus scrofa | |
| additional information | - |
additional information | overview | Bos taurus | |
| additional information | - |
additional information | overview | Crithidia fasciculata | |
| additional information | - |
additional information | overview | Lacticaseibacillus casei | |
| additional information | - |
additional information | overview | Enterococcus faecium | |
| additional information | - |
additional information | overview | vertebrata | |
| additional information | - |
additional information | overview | protozoa | |
| additional information | - |
additional information | Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes | Gallus gallus | |
| additional information | - |
additional information | Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes | Bacteria | |
| additional information | - |
additional information | Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes | Mus musculus | |
| additional information | - |
additional information | Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes | Escherichia coli | |
| additional information | - |
additional information | Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes | Homo sapiens | |
| additional information | - |
additional information | Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes | Sus scrofa | |
| additional information | - |
additional information | Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes | Bos taurus | |
| additional information | - |
additional information | Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes | Crithidia fasciculata | |
| additional information | - |
additional information | Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes | Lacticaseibacillus casei | |
| additional information | - |
additional information | Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes | Enterococcus faecium | |
| additional information | - |
additional information | Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes | vertebrata | |
| additional information | - |
additional information | Km of enzymes with decreased binding of folate and antagonists and of drug-sensitive enzymes | protozoa |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| organic mercurials | - |
Mammalia | |
| organic mercurials | - |
Lacticaseibacillus casei | |
| organic mercurials | animal enzyme: activated, bacterial enzyme: unaffected or inhibited | Gallus gallus | |
| organic mercurials | animal enzyme: activated, bacterial enzyme: unaffected or inhibited | Mus musculus | |
| organic mercurials | animal enzyme: activated, bacterial enzyme: unaffected or inhibited | Homo sapiens | |
| organic mercurials | animal enzyme: activated, bacterial enzyme: unaffected or inhibited | Sus scrofa | |
| organic mercurials | animal enzyme: activated, bacterial enzyme: unaffected or inhibited | Bos taurus |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 18250 | - |
MB 1428, amino acid sequence | Escherichia coli |
| 18300 | - |
amino acid sequence | Lacticaseibacillus casei |
| 19600 | - |
isoenzyme II, amino acid sequence | Enterococcus faecium |
| 21450 | - |
amino acid sequence | Sus scrofa |
| 21450 | - |
amino acid sequence | Bos taurus |
| 21460 | - |
methotrexate resistant L1210(R) cells, amino acid sequence | Mus musculus |
| 21650 | - |
amino acid sequence | Gallus gallus |
| 56700 | - |
2 * 56700, bifunctional enzyme: thymidylate synthase-dihydrofolate reductase, SDS-PAGE | Crithidia fasciculata |
| 107000 | - |
bifunctional enzyme: thymidylate synthase-dihydrofolate reductase | Crithidia fasciculata |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Bacteria | - |
overview | - |
| Bos taurus | - |
- |
- |
| Crithidia fasciculata | - |
bifunctional enzyme: dihydrofolate reductase-thymidylate synthase EC 2.1.1.45 | - |
| Enterococcus faecium | - |
- |
- |
| Escherichia coli | - |
various strains | - |
| Gallus gallus | - |
- |
- |
| Homo sapiens | - |
methotrexate-resistant WIL-2 lymphoblastoid cells | - |
| Lacticaseibacillus casei | - |
- |
- |
| Mammalia | - |
cultured mammalian cells, overview | - |
| Mus musculus | - |
L1210 lymphoma cells, amethopterin-resistant | - |
| protozoa | - |
overview | - |
| Streptococcus pneumoniae | - |
methotrexate-resistant form | - |
| Sus scrofa | - |
- |
- |
| Tequatrovirus T4 | - |
- |
- |
| vertebrata | - |
overview | - |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
- |
Escherichia coli |
- |
Tequatrovirus T4 |
Reaction
| Reaction | Comment | Organism | Reaction ID |
|---|---|---|---|
| 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 | Enterococcus faecium | |
| 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 |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| liver | - |
Gallus gallus | - |
| liver | - |
Mus musculus | - |
| liver | - |
Sus scrofa | - |
| liver | - |
Bos taurus | - |
Specific Activity [micromol/min/mg]
| Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
|---|---|---|---|
| 11 | - |
methotrexate resistant cells, L1210 (R), 25°C | Mus musculus |
| 12 | - |
30°C | Lacticaseibacillus casei |
| 14 | - |
chicken liver, 28°C | Gallus gallus |
| 15 | - |
human WIL2 (M4) cells, 22°C | Homo sapiens |
| 26 | - |
bovine liver, 28°C | Bos taurus |
| 27 | - |
methotrexate resistant cells, sarcoma 180 (AT/3000), 37°C | Mammalia |
| 36 | - |
methotrexate resistant, 23°C | Escherichia coli |
| 36 | - |
liver, 30°C | Sus scrofa |
| 45 | - |
- |
Escherichia coli |
| 45 | - |
methotrexate resistant cells, isoenzyme II, 37°C | Enterococcus faecium |
| 55 | - |
trimethoprim resistant, 30°C | Escherichia coli |
| 60 | - |
human KB cells, 37°C | Homo sapiens |
| 300 | - |
isoenzyme I | Enterococcus faecium |
| 300 | - |
25°C | Enterococcus faecium |
| 300 | - |
methotrexate resistant cells | Enterococcus faecium |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 7,8-dihydrofolate + NADPH | - |
Gallus gallus | 5,6,7,8-tetrahydrofolate + NADP+ | - |
? | |
| 7,8-dihydrofolate + NADPH | - |
Mammalia | 5,6,7,8-tetrahydrofolate + NADP+ | - |
? | |
| 7,8-dihydrofolate + NADPH | - |
Bacteria | 5,6,7,8-tetrahydrofolate + NADP+ | - |
? | |
| 7,8-dihydrofolate + NADPH | - |
Mus musculus | 5,6,7,8-tetrahydrofolate + NADP+ | - |
? | |
| 7,8-dihydrofolate + NADPH | - |
Escherichia coli | 5,6,7,8-tetrahydrofolate + NADP+ | - |
? | |
| 7,8-dihydrofolate + NADPH | - |
Homo sapiens | 5,6,7,8-tetrahydrofolate + NADP+ | - |
? | |
| 7,8-dihydrofolate + NADPH | - |
Sus scrofa | 5,6,7,8-tetrahydrofolate + NADP+ | - |
? | |
| 7,8-dihydrofolate + NADPH | - |
Bos taurus | 5,6,7,8-tetrahydrofolate + NADP+ | - |
? | |
| 7,8-dihydrofolate + NADPH | - |
Crithidia fasciculata | 5,6,7,8-tetrahydrofolate + NADP+ | - |
? | |
| 7,8-dihydrofolate + NADPH | - |
Lacticaseibacillus casei | 5,6,7,8-tetrahydrofolate + NADP+ | - |
? | |
| 7,8-dihydrofolate + NADPH | - |
Enterococcus faecium | 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+ | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| dimer | - |
Bacteria |
| dimer | - |
Escherichia coli |
| dimer | 2 * 56700, bifunctional enzyme: thymidylate synthase-dihydrofolate reductase, SDS-PAGE | Crithidia fasciculata |
| monomer | - |
Bacteria |
| monomer | - |
Tequatrovirus T4 |
| monomer | 1 * 21650, amino acid sequence | Gallus gallus |
| monomer | 1 * 21450, amino acid sequence | Sus scrofa |
| monomer | 1 * 21450, amino acid sequence | Bos taurus |
| monomer | 1 * 21460, methotrexate resistant L1210 (R) cells, amino acid sequence | Mus musculus |
| monomer | 1 * 18250, MB 1428, amino acid sequence | Escherichia coli |
| monomer | 1 * 19600, isoenzyme II, amino acid sequence | Enterococcus faecium |
| monomer | 1 * 18300, amino acid sequence | Lacticaseibacillus casei |
| More | - |
Crithidia fasciculata |
| More | overview | Bacteria |
| More | overview | Tequatrovirus T4 |
| 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 |
|---|---|---|---|---|---|
| 3.67 | - |
NADPH | pH 6.5 | Lacticaseibacillus casei | |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 4 | - |
methotrexate resistant cells L1210 (R), sarcoma 180 (AT/300), 2 optima: pH 4 and pH 7.5 | Mammalia |
| 4 | - |
methotrexate resistant cells L1210 (R), sarcoma 180 (AT/300), 2 optima: pH 4 and pH 7.5 | Mus musculus |
| 4 | - |
7,8-dihydrofolate + NADPH, 2 optima: pH 4 and pH 7.4 | Gallus gallus |
| 4 | - |
human WIL 2 cell line, 2 optima: pH 4 and pH 7.3-8.3 | Homo sapiens |
| 4.8 | 5 | - |
Bos taurus |
| 5 | - |
2 optima: pH 5 and pH 7.6 | Sus scrofa |
| 5.8 | - |
7,8-dihydrofolate, isoenzyme II, methotrexate resistant cells | Enterococcus faecium |
| 6.5 | - |
- |
Escherichia coli |
| 6.5 | - |
- |
Lacticaseibacillus casei |
| 6.5 | - |
isoenzyme I, methotrexate resistant cells | Enterococcus faecium |
| 6.8 | - |
- |
Crithidia fasciculata |
| 6.8 | - |
MB 1328 | Escherichia coli |
| 7.2 | 8.2 | KB cells, 2 optima: below pH 5.0 and pH 7.2-8.2 | Homo sapiens |
| 7.3 | 8.3 | WIL2 (M4) cells, 2 optima: pH 4 and pH 7.3-8.3 | Homo sapiens |
| 7.4 | - |
7,8-dihydrofolate + NADPH, 2 optima: pH 4.0 and pH 7.4 | Gallus gallus |
| 7.5 | - |
- |
Homo sapiens |
| 7.5 | - |
methotrexate resistant cells, L1210(R), sarcoma 180 (AT/30000), 2 optima: pH 4.0 and pH 7.5 | Mammalia |
| 7.5 | - |
methotrexate resistant cells, L1210(R), sarcoma 180 (AT/30000), 2 optima: pH 4.0 and pH 7.5 | Mus musculus |
| 7.6 | - |
- |
Escherichia coli |
| 7.6 | - |
- |
Sus scrofa |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| NADPH | - |
Gallus gallus | |
| NADPH | - |
Mammalia | |
| NADPH | - |
Mus musculus | |
| NADPH | - |
Escherichia coli | |
| NADPH | - |
Homo sapiens | |
| NADPH | - |
Sus scrofa | |
| NADPH | - |
Bos taurus | |
| NADPH | - |
Crithidia fasciculata | |
| NADPH | - |
Streptococcus pneumoniae | |
| NADPH | - |
Lacticaseibacillus casei | |
| NADPH | - |
Enterococcus faecium | |
| NADPH | - |
Tequatrovirus T4 | |
| NADPH | interaction study | Bacteria | |
| NADPH | interaction study | vertebrata | |
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 |
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