This represents the catalytic domain of 5,10-methylenetetrahydrofolate reductase from prokaryotes and methylenetetrahydrofolate reductase (MTHFR) from eukaryotes (). Both convert 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolate.Mammalian and yeast MTHFRs are homodimers in which each subunit contains an N-terminal catalytic domain, and a C-terminal regulatory domain to which the allosteric inhibitor adenosylmethionine binds []. NADPH is the preferred reductant. In humans, there are several clinically significant mutations in MTHFR that result in hyperhomocysteinemia, which is a risk factor for the development of cardiovascular disease [].The bacterial enzyme is a homotetramer. MTHFRs of enteric bacteria comprise shorter chains around 300 residues in length. Their sequences can be aligned with the N-terminal catalytic domains of the eukaryotic MTHFRs []. Escherichia coli MTHFR, along with plant MTHFRs, prefer NADHs as the source of reducing equivalents []. The structure of E. coli MTHFR is known to be a TIM barrel [].
