Recombinant Human MTHFD1 protein

Methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) is a pivotal enzyme in folate-mediated one-carbon metabolism, a metabolic network essential for nucleotide synthesis, methylation reactions, and cellular redox balance. It is a trifunctional protein harboring three enzymatic activities: 5.10-methylenetetrahydrofolate dehydrogenase, 5.10-methenyltetrahydrofolate cyclohydrolase, and 10-formyltetrahydrofolate synthetase. These activities collectively mediate the interconversion of one-carbon-substituted folate derivatives, enabling the transfer of carbon units for purine and thymidylate biosynthesis. MTHFD1 exists as cytoplasmic and mitochondrial isoforms generated via alternative splicing, with the cytoplasmic form predominantly supporting cytosolic one-carbon metabolism. Dysregulation of MTHFD1 has been implicated in developmental disorders, cardiovascular diseases, and cancer, underscoring its role in cellular proliferation and genome stability. Recombinant MTHFD1 proteins are typically produced in bacterial (e.g., E. coli) or mammalian expression systems to preserve enzymatic activity. These recombinant variants facilitate structural studies, inhibitor screening, and functional analyses of genetic variants. Recent research focuses on MTHFD1 as a therapeutic target, particularly in cancers reliant on enhanced folate metabolism. Engineered truncations or mutations in recombinant proteins help dissect domain-specific functions, while crystallography studies using recombinant MTHFD1 have revealed substrate-binding mechanisms. Its dual role in supporting nucleotide synthesis and methyl group provision makes recombinant MTHFD1 a critical tool for investigating metabolic vulnerabilities in rapidly dividing cells and designing targeted therapies.