<p>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 (<db_xref db="EC" dbkey="1.5.1.5"/>), methenyl-THF cyclohydrolase (<db_xref db="EC" dbkey="3.5.4.9"/>)and formyl-THF synthetase (<db_xref db="EC" dbkey="6.3.4.3"/>) [<cite idref="PUB00000304"/>, <cite idref="PUB00000651"/>]. The dehydrogenase and cyclohydrolaseactivities are expressed by a variety of multifunctional enzymes, including the tri-functional eukaryoticC1-tetrahydrofolate synthase [<cite idref="PUB00000304"/>]; a bifunctional eukaryotic mitochondrial protein; and thebifunctional <taxon tax_id="562">Escherichia coli</taxon> folD protein [<cite idref="PUB00000304"/>, <cite idref="PUB00000651"/>]. Methylene-tetrahydrofolate dehydrogenase andmethenyltetrahydrofolate cyclo-hydrolase share an overlapping active site [<cite idref="PUB00000304"/>], and as such areusually located together in proteins, acting in tandem on the carbon-nitrogen bonds of substrates otherthan peptide bonds.</p><p>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.</p>