Molecular structure of a 5,10-methylenetetrahydrofolate dehydrogenase from the silkworm .

The enzyme 5,10-methylenetetrahydrofolate dehydrogenase (MTHFD) is essential for the production of certain amino acids (glycine, serine, and methionine) and nucleic acids (thymidylate and purine). Here, we identified a cDNA encoding this enzyme from the silkworm . The recombinant MTHFD (bmMTHFD) expressed in recognized 5,10-methylenetetrahydrofolate and 5,10-methenyltetrahydrofolate as substrate in the presence of NADP as well as NAD . The bmMTHFD structure was determined at a resolution of 1.75 Å by X-ray crystallography. Site-directed mutagenesis indicated that the amino acid residue Tyr49 contributed to its catalytic activity. Our findings provide insight into the mechanism underlying the activity of MTHFD from and potentially other insects and may therefore facilitate the development of inhibitors specific to MTHFD as insecticides.