EC Number | Cloned (Comment) | Organism |
---|---|---|
1.5.1.5 | the wild type and R653Q mutant pBKeDCS constructs are transformed into Escherichia coli BL21 DE3 to express the full-length protein | Homo sapiens |
3.5.4.9 | the wild type and R653Q mutant pBKeDCS constructs are transformed into Escherichia coli BL21 DE3 to express the full-length protein | Homo sapiens |
6.3.4.3 | the wild type and R653Q mutant pBKeDCS constructs are transformed into Escherichia coli BL21 DE3 to express the full-length protein | Homo sapiens |
EC Number | Protein Variants | Comment | Organism |
---|---|---|---|
1.5.1.5 | R653Q | mutant enzyme has normal substrate affinity but a 36% reduction in half-life at 42°C | Homo sapiens |
3.5.4.9 | R653Q | mutant enzyme only affects the synthetase activity | Homo sapiens |
6.3.4.3 | R653Q | mutant enzyme has normal substrate affinity but a 36% reduction in half-life at 42°C, the mutation reduces the metabolic activity of MTHFD1 within cells: formate incorporation into DNA in murine Mthfd1 knockout cells transfected with Arg653Gln is reduced by 26%, compared to cells transfected with wild-type protein, the mutant may increase the risk for neural tube defects, under ideal storage and standard assay conditions, the synthetase activity of MTHFD1 is unaffected by the R653Q mutation | Homo sapiens |
EC Number | Inhibitors | Comment | Organism | Structure |
---|---|---|---|---|
6.3.4.3 | ADP | - |
Homo sapiens | |
6.3.4.3 | pteroylpentaglutamate | - |
Homo sapiens |
EC Number | KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|---|
6.3.4.3 | 0.0286 | - |
ATP | mutant R653Q | Homo sapiens | |
6.3.4.3 | 0.0302 | - |
ATP | wild type | Homo sapiens | |
6.3.4.3 | 0.0367 | - |
formate | wild type | Homo sapiens | |
6.3.4.3 | 0.0371 | - |
formate | mutant R653Q | Homo sapiens | |
6.3.4.3 | 0.333 | - |
tetrahydrofolate | mutant R653Q | Homo sapiens | |
6.3.4.3 | 0.364 | - |
tetrahydrofolate | wild type | Homo sapiens |
EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|---|
1.5.1.5 | 5,10-methylene tetrahydrofolate + NADP+ | Homo sapiens | dehydrogenase activity of MTHFD1 | 5,10-methenyltetrahydrofolate + NADPH | - |
r | |
1.5.1.5 | additional information | Homo sapiens | (MTHFD1) is a trifunctional enzyme that interconverts tetrahydrofolate derivatives for nucleotide synthesis | ? | - |
? | |
3.5.4.9 | 5,10-methenyltetrahydrofolate + H2O | Homo sapiens | cyclodehydrolase activity of MTHFD1 | 10-formyltetrahydrofolate + ? | - |
r | |
3.5.4.9 | additional information | Homo sapiens | MTHFD1 is a trifunctional enzyme that interconverts tetrahydrofolate derivatives for nucleotide synthesis | ? | - |
? | |
6.3.4.3 | formate + ATP + tetrahydrofolate | Homo sapiens | synthetase activity of MTHFD1 | 10-formyltetrahydrofolate + ADP + phosphate | - |
? | |
6.3.4.3 | additional information | Homo sapiens | (MTHFD1) is a trifunctional enzyme that interconverts tetrahydrofolate derivatives for nucleotide synthesis | ? | - |
? |
EC Number | Organism | UniProt | Comment | Textmining |
---|---|---|---|---|
1.5.1.5 | Homo sapiens | P11586 | - |
- |
3.5.4.9 | Homo sapiens | P11586 | - |
- |
6.3.4.3 | Homo sapiens | P11586 | - |
- |
EC Number | Purification (Comment) | Organism |
---|---|---|
1.5.1.5 | by anion-exchange chromatography | Homo sapiens |
3.5.4.9 | by anion-exchange chromatography | Homo sapiens |
6.3.4.3 | by anion-exchange chromatography | Homo sapiens |
EC Number | Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
---|---|---|---|---|
1.5.1.5 | 13.2 | - |
dehydrogenase activity of the wild type enzyme | Homo sapiens |
1.5.1.5 | 13.9 | - |
dehydrogenase activity of the mutant R653Q | Homo sapiens |
6.3.4.3 | additional information | - |
100.2% activity of mutant R653Q after heating at 42°C for 90 min, in 7.5% glycerol and 0.35 mM folate pentaglutamate | Homo sapiens |
6.3.4.3 | additional information | - |
102% activity of wild type enzyme after heating at 42°C for 90 min, in 7.5% glycerol and 0.35 mM folate pentaglutamate | Homo sapiens |
6.3.4.3 | additional information | - |
57.4% activity of mutant R653Q, without adding of any cofactor, after heating at 42°C for 90 min, in 7.5% glycerol | Homo sapiens |
6.3.4.3 | additional information | - |
72.3% activity of wild type enzyme, without adding of any cofactor, after heating at 42°C for 90 min, in 7.5% glycerol | Homo sapiens |
6.3.4.3 | additional information | - |
80.5% activity of mutant R653Q after heating at 42°C for 90 min, in 7.5% glycerol, 1.2 mM MgCl, 0.6 mM ATP | Homo sapiens |
6.3.4.3 | additional information | - |
88.2% activity of wild type enzyme after heating at 42°C for 90 min, in 7.5% glycerol, 1.2 mM MgCl, 0.6 mM ATP | Homo sapiens |
6.3.4.3 | additional information | - |
enzyme knock-out cells are transfected with either wild type or R653Q mutant and their ability to synthesize purines is assessed by a 14C-formate incorporation assay, the cells expressing the R653Q variant incorporate only 74% of wild-type levels of formate into DNA, the R653Q protein appears to have a significant impact on cellular nucleotide metabolism | Homo sapiens |
6.3.4.3 | 23 | - |
synthetase activity of the wild type enzyme | Homo sapiens |
6.3.4.3 | 23.8 | - |
synthetase activity of the mutant R653Q | Homo sapiens |
EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|---|
1.5.1.5 | 5,10-methylene tetrahydrofolate + NADP+ | dehydrogenase activity of MTHFD1 | Homo sapiens | 5,10-methenyltetrahydrofolate + NADPH | - |
r | |
1.5.1.5 | additional information | (MTHFD1) is a trifunctional enzyme that interconverts tetrahydrofolate derivatives for nucleotide synthesis | Homo sapiens | ? | - |
? | |
3.5.4.9 | 5,10-methenyltetrahydrofolate + H2O | cyclodehydrolase activity of MTHFD1 | Homo sapiens | 10-formyltetrahydrofolate + ? | - |
r | |
3.5.4.9 | additional information | MTHFD1 is a trifunctional enzyme that interconverts tetrahydrofolate derivatives for nucleotide synthesis | Homo sapiens | ? | - |
? | |
6.3.4.3 | (R,S)-tetrahydrofolate + ATP + formate | - |
Homo sapiens | ? | - |
r | |
6.3.4.3 | formate + ATP + tetrahydrofolate | synthetase activity of MTHFD1 | Homo sapiens | 10-formyltetrahydrofolate + ADP + phosphate | - |
? | |
6.3.4.3 | additional information | (MTHFD1) is a trifunctional enzyme that interconverts tetrahydrofolate derivatives for nucleotide synthesis | Homo sapiens | ? | - |
? |
EC Number | Synonyms | Comment | Organism |
---|---|---|---|
1.5.1.5 | methylenetetrahydrofolate dehydrogenase | - |
Homo sapiens |
1.5.1.5 | methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase | - |
Homo sapiens |
1.5.1.5 | MTHFD1 | - |
Homo sapiens |
3.5.4.9 | methenyltetrahydrofolate cyclohydrolase | - |
Homo sapiens |
3.5.4.9 | methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase | - |
Homo sapiens |
3.5.4.9 | MTHFD1 | - |
Homo sapiens |
6.3.4.3 | Formyltetrahydrofolate synthetase | - |
Homo sapiens |
6.3.4.3 | methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase | - |
Homo sapiens |
6.3.4.3 | MTHFD1 | - |
Homo sapiens |
EC Number | Temperature Stability Minimum [°C] | Temperature Stability Maximum [°C] | Comment | Organism |
---|---|---|---|---|
6.3.4.3 | additional information | - |
thermolability is reduced by magnesium adenosine triphosphate and eliminated by the substrate analog folate pentaglutamate, suggesting that folate status may modulate impact of the variant R653Q | Homo sapiens |
EC Number | Cofactor | Comment | Organism | Structure |
---|---|---|---|---|
1.5.1.5 | NADP+ | - |
Homo sapiens | |
6.3.4.3 | ATP | - |
Homo sapiens |
EC Number | Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|---|
6.3.4.3 | 0.0296 | - |
pteroylpentaglutamate | wild type enzyme | Homo sapiens | |
6.3.4.3 | 0.0328 | - |
pteroylpentaglutamate | mutant R653Q | Homo sapiens | |
6.3.4.3 | 0.0338 | - |
ADP | mutant R653Q | Homo sapiens | |
6.3.4.3 | 0.0364 | - |
ADP | wild type enzyme | Homo sapiens |