InterPro

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 different oxidation states by methylene-THF dehydrogenase (EC:1.5.1.5), methenyl-THF cyclohydrolase (EC:3.5.4.9) and formyl-THF synthetase (EC:6.3.4.3) [PMID: 2541774, PMID: 8485162]. The dehydrogenase and cyclohydrolase activities are expressed by a variety of multifunctional enzymes, including the tri-functional eukaryotic C1-tetrahydrofolate synthase [PMID: 2541774]; a bifunctional eukaryotic mitochondrial protein; and the bifunctional Escherichia coli folD protein [PMID: 2541774, PMID: 8485162]. Methylene-tetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclo-hydrolase share an overlapping active site [PMID: 2541774], and as such are usually located together in proteins, acting in tandem on the carbon-nitrogen bonds of substrates other than peptide bonds.

The sequence of the dehydrogenase/cyclohydrolase domain is highly conserved in all forms of the enzyme. This entry contains two conserved signature patterns; the first one is located in the N-terminal part of these enzymes and contains three acidic residues. The second pattern is a highly conserved sequence of 9 amino acids, which is located in the C-terminal section.