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Literature summary for 1.5.1.53 extracted from

  • Froese, D.; Kopec, J.; Rembeza, E.; Bezerra, G.; Oberholzer, A.; Suormala, T.; Lutz, S.; Chalk, R.; Borkowska, O.; Baumgartner, M.; Yue, W.
    Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition (2018), Nat. Commun., 9, 2261 .
    View publication on PubMedView publication on EuropePMC

Crystallization (Commentary)

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

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

Inhibitors Comment Organism Structure
S-adenosyl-L-methionine
-
Homo sapiens

KM Value [mM]

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

Organism UniProt Comment Textmining
Homo sapiens P42898
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein phosphorylation of up to 11 residues. Phosphorylation does not alter MTHFR kinetic parameters Homo sapiens

Substrates and Products (Substrate)

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 [1/s]

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

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 [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