Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, also known as MTHFD2, is a nuclear-encoded mitochondrial enzyme with bifunctional activities. It possesses both methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase activities. This enzyme plays a crucial role in the folate metabolism pathway, which is essential for the synthesis of nucleotides and amino acids.
MTHFD2 functions as a homodimer and is unique in its absolute requirement for magnesium and inorganic phosphate . The enzyme is involved in the conversion of methylenetetrahydrofolate to methenyltetrahydrofolate, which is a critical step in the folate cycle. This cycle is vital for the production of purines and thymidylate, which are necessary for DNA synthesis and repair.
MTHFD2 is highly expressed in rapidly proliferating cells, such as cancer cells, and is considered a potential oncogene due to its strong association with poor prognosis and high levels of immune infiltrates in various cancers . The expression of MTHFD2 is regulated by several factors, including nutrient availability and cellular stress.
Recombinant human MTHFD2 is produced using Escherichia coli expression systems and is typically purified to a high degree of purity (>95%) suitable for various applications such as SDS-PAGE and mass spectrometry . The recombinant protein is often tagged with a His-tag at the N-terminus to facilitate purification and detection.
Recombinant MTHFD2 is used in research to study its role in folate metabolism, cancer biology, and potential as a therapeutic target. It is also utilized in biochemical assays to investigate its enzymatic activities and interactions with other proteins and small molecules.
Due to its elevated expression in cancer cells and its association with poor prognosis, MTHFD2 is being explored as a biomarker for cancer diagnosis and prognosis. Additionally, targeting MTHFD2 with specific inhibitors is being investigated as a potential therapeutic strategy for cancer treatment .