Enzyme
1.5.1.5 - Methylenetetrahydrofolate dehydrogenase (NADP(+))
Alternative Name(s)
There are no alternative names for this Enzyme
Catalytic Activity
(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NADP(+) = 5,10-methenyltetrahydrofolate + NADPH
Cofactors
There are no Cofactors for this Enzyme
Reaction Mechanism
Enzymes involved in tetrahydrofolate metabolism are of particular pharmaceutical interest, as their function is crucial for amino acid and DNA biosynthesis.
In eukaryotes, the enzyme that performs this reaction occurs as a trifunctional enzyme that also has methylenetetrahydrofolate dehydrogenase (NADP+) (EC 1.5.1.5) and formate-tetrahydrofolate ligase (EC 6.3.4.3) activity. In some prokaryotes, it occurs as a bifunctional enzyme that also has dehydrogenase (EC 1.5.1.5) activity or formiminotetrahydrofolate cyclodeaminase (EC 4.3.1.4) activity. This particular entry represents the dehydrogenase activity.
Although the human protein represented here is actually trifunctional, the representative PDB structure only contains the dehydrogenase (D) and cyclohydrolase (C) domains, which have an overlapping active site (as determined by chemical modification and kinetic studies).
In eukaryotes, the enzyme that performs this reaction occurs as a trifunctional enzyme that also has methylenetetrahydrofolate dehydrogenase (NADP+) (EC 1.5.1.5) and formate-tetrahydrofolate ligase (EC 6.3.4.3) activity. In some prokaryotes, it occurs as a bifunctional enzyme that also has dehydrogenase (EC 1.5.1.5) activity or formiminotetrahydrofolate cyclodeaminase (EC 4.3.1.4) activity. This particular entry represents the dehydrogenase activity.
Although the human protein represented here is actually trifunctional, the representative PDB structure only contains the dehydrogenase (D) and cyclohydrolase (C) domains, which have an overlapping active site (as determined by chemical modification and kinetic studies).
5,10-methylene-tetrahydrofolate is converted to 5,10-methenyltetrahydrofolate. The mechanism involves hydride transfer from the substrate to NADP+.
Catalytic Residues
| AA | Uniprot | Uniprot Resid | PDB | PDB Resid |
|---|---|---|---|---|
| Gln | P11586 | 100 | 1a4i | 100 |
| Lys | P11586 | 56 | 1a4i | 56 |
| Asp | P11586 | 125 | 1a4i | 125 |
Reaction Parameters
There are no kinetic parameters information for this Enzyme
Associated Proteins
Citations
- Folate trapping is lethal to cancer cells.
- Amlodipine downregulates gene expression that involved in the signaling pathways of coagulation process in COVID-19 patients: An observational clinical study.
- MTHFD1 is critical for the negative regulation of retinoic acid receptor signalling in anencephaly.
- Biallelic MTHFD1 variants presenting as severe combined immunodeficiency.
- Mitochondrial one-carbon metabolic enzyme MTHFD2 facilitates mammary gland development during pregnancy.
- MTHFD1 Regulates the NADPH Redox Homeostasis in MYCN-amplified Neuroblastoma
- Apollo-NADP+ reveals in vivo adaptation of NADPH/NADP+ metabolism in electrically activated pancreatic β cells.
- The negative effect of G1958A polymorphism on MTHFD1 protein stability and HCC growth.
- Pharmacological targeting of one‑carbon metabolism as a novel therapeutic strategy for glioblastoma.
- Antiviral strategies: What can we learn from natural reservoirs?
- Targeting serine-glycine-one-carbon metabolism as a vulnerability in cancers.