Methionine synthases catalyze the transfer of a methyl group from the tertiary amino group of 5-methyl-tetrahydrofolate (5-methyl-THF) to the sulfhydryl group of l-homocysteine (Hcy) to synthesize l-methionine, and regenerating THF. There are two types of
MK-2206 synthase: (1) cobalamin-dependent methionine synthase and (2) cobalamin-independent methionine synthase. The former, encoded in Escherichia coli by the MetH gene, makes use of a cobalamin prosthetic group for methyl transfer. The cobalamin-independent form, encoded in E. coli by the MetE gene, performs direct methyl transfer [1]. The MetH gene homolog is seen in animals (including humans), eubacteria, and eukaryotes, while the MetE homolog is seen in plants, insects, fungi, archaea, and eubacteria, which are deficient in vitamin B12. In yeast, and other fungi, the gene encoding the B12-independent enzyme is referred to as MET6 and the corresponding protein is Met6p. Although both of these
enzymes carry out the same overall reaction, there is no sequence similarity between the two [2]. The MetH gene product is a 140 kDa protein consisting of four distinct domains for binding Hcy, 5-methyl-THF, cobalamin, and S-adenosylmethionine [3]. The MetE gene product is an 84 kDa protein; X-ray structures have been solved for the enzymes from Arabidopsis thaliana and Thermatoga maritima [4] and [5].
