InterPro domain: IPR020630

Enzymes that participate in the transfer of one-carbon units require the coenzyme tetrahydrofolate (THF).Various reactions generate one-carbon derivatives of THF, which can be interconverted between differentoxidation states by methylene-THF dehydrogenase ( 1.5.1.5 ), methenyl-THF cyclohydrolase ( 3.5.4.9 )and formyl-THF synthetase ( 6.3.4.3 ) [ 1 , 2 ]. The dehydrogenase and cyclohydrolaseactivities are expressed by a variety of multifunctional enzymes, including the tri-functional eukaryoticC1-tetrahydrofolate synthase [ 3 ]; a bifunctional eukaryotic mitochondrial protein; and thebifunctional Escherichia coli folD protein [ 3 , 3 ]. Methylene-tetrahydrofolate dehydrogenase andmethenyltetrahydrofolate cyclo-hydrolase share an overlapping active site [ 3 ], and as such areusually located together in proteins, acting in tandem on the carbon-nitrogen bonds of substrates otherthan peptide bonds.

This entry represents the N-terminal catalytic domain of these enzymes.

1. Site-directed mutagenesis of yeast C1-tetrahydrofolate synthase: analysis of an overlapping active site in a multifunctional enzyme. Biochemistry 28, 2099-106
2. The isolation and characterization of a Drosophila gene encoding a putative NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase. Biochim. Biophys. Acta 1173, 94-8