The interconversion of two major one-carbon donors, methylene and methenyl groups, occurs through the sequential activities of NAD(P)-dependent methylenetetrahydrofolate dehydrogenase (MTHFD) and methenyltetrahydrofolate cyclohydrolase (MTHFC). These activities frequently coexist as a part of a bifunctional enzyme in prokaryotes. In higher organisms, MTHFR and MTHFC are often linked together with another protein, formyl-THF synthetase (FTHFS) and operate as a trifunctional enzyme. The structure of the FolD bifunctional protein, a predicted MTHFR/MTHFC from Campylobacter jejuni with NAD determined to 2.23 A. The structure is a dimer with each subunit consisting of two α/β domains and containing a wide, largely hydrophobic cleft formed between the two domains.
beta-6-hydroxy-1,4,5,6-tetrhydronicotinamide adenine di nucleotide