Abstract
Two genes encoding proteins with methionine synthase activity are found in Escherichia coli. Both enzymes use methyltetrahydrofolate as a methyl donor to catalyze the conversion of homocysteine to methionine, as shown below:
The metH gene encodes a cobalamin-dependent methionine synthase (MetH). This protein is monomelic, with a deduced molecular weight of 136,055.1 It can use CH3-H4PteGlu1 as a substrate, and requires a reducing system and AdoMet for activation.2,3 The metE gene encodes a cobalamin-independent methionine synthase that requires methyltetrahydrofolate substrates with at least two glutamyl residues and is completely inactive with CH3-H4PteGlu1.4 This enzyme shows no requirement for reductive activation, but does require phosphate ion and magnesium for optimal rates of catalysis.5 It has a deduced molecular weight of 84,654,6 in good agreement with the value of 84,000 obtained by ultracentrifugation of the native enzyme.5 Both the metH 1,7,8 and metE 6,9genes have been sequenced, and their coding sequences show no detectable homologies. Thus these two proteins appear to have evolved independently to perform highly similar methyl transfers from N5 of methyltetrahydrofolate to the sulfur of homocysteine.
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References
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Drummond, J.T., Matthews, R.G. (1993). Cobalamin-Dependent and Cobalamin-Independent Methionine Synthases in Escherichia coli: Two Solutions to the Same Chemical Problem. In: Ayling, J.E., Nair, M.G., Baugh, C.M. (eds) Chemistry and Biology of Pteridines and Folates. Advances in Experimental Medicine and Biology, vol 338. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2960-6_142
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