Crystallization (Comment) | Organism |
---|---|
structure of human MTHFR at 2.5 A resolution reveals a unique architecture, appending the well-conserved catalytic TIM-barrel to a eukaryote-only SAM-binding domain. The latter domain provides the predominant interface for MTHFR homo-dimerization and positions the N-terminal serine-rich phosphorylation region near the C-terminal SAM-binding domain. MTHFR phosphorylation, identified on 11 N-terminal residues (16 in total), increases sensitivity to SAM binding and inhibition. The 25-amino-acid inter-domain linker enables conformational plasticity and may be a key mediator of SAM regulation | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | expression of a truncated protein, residues 38-644, lacking the phosphorylation sites. Nonphosphorylated MHTFR has similar kinetic values as wild-type | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
S-adenosyl-L-methionine | - |
Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0224 | - |
5,10-methylenetetrahydrofolate | wild-type, pH 6.6, temperature not specified in the publication | Homo sapiens | |
0.0235 | - |
NADPH | truncated protein, residues 38-644, pH 6.6, temperature not specified in the publication | Homo sapiens | |
0.0255 | - |
5,10-methylenetetrahydrofolate | truncated protein, residues 38-644, pH 6.6, temperature not specified in the publication | Homo sapiens | |
0.0355 | - |
NADPH | wild-type, pH 6.6, temperature not specified in the publication | Homo sapiens | |
2.16 | - |
NADH | truncated protein, residues 38-644, pH 6.6, temperature not specified in the publication | Homo sapiens | |
3.76 | - |
NADH | wild-type, pH 6.6, temperature not specified in the publication | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P42898 | - |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
phosphoprotein | phosphorylation of up to 11 residues. Phosphorylation does not alter MTHFR kinetic parameters | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
5,10-methylenetetrahydrofolate + NADH + H+ | - |
Homo sapiens | 5-methyltetrahydrofolate + NAD+ | - |
? | |
5,10-methylenetetrahydrofolate + NADPH + H+ | - |
Homo sapiens | 5-methyltetrahydrofolate + NADP+ | - |
? |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
40.7 | - |
5,10-methylenetetrahydrofolate | wild-type, pH 6.6, temperature not specified in the publication | Homo sapiens | |
51.4 | - |
5,10-methylenetetrahydrofolate | truncated protein, residues 38-644, pH 6.6, temperature not specified in the publication | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
FAD | - |
Homo sapiens | |
NADH | NADPH is about 100fold preferred over NADH | Homo sapiens | |
NADPH | - |
Homo sapiens |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0025 | - |
S-adenosyl-L-methionine | wild-type, pH 6.6, temperature not specified in the publication | Homo sapiens | |
0.021 | - |
S-adenosyl-L-methionine | truncated protein, residues 38-644, pH 6.6, temperature not specified in the publication | Homo sapiens |