Proofreading and the evolution of a methyl donor function. Cyclization of methionine to S-methyl homocysteine thiolactone by Escherichia coli methionyl-tRNA synthetase.

A cyclic sulfonium compound, S-methyl homocysteine thiolactone (SMHT), is formed from methionine during in vitro tRNA aminoacylation catalyzed by Escherichia coli methionyl-tRNA synthetase. The mechanism of SMHT formation involves enzymatic deacylation of Met-tRNA (k = 0.06 s-1) and, to a lesser extent, Met-AMP (k = 0.02 s-1). Cyclization of methionine, reminiscent of cyclization of homocysteine during editing, illustrates the limited ability of methionyl-tRNA synthetase to discriminate against the cognate methionine at the editing site designed for the noncognate homocysteine. In early stages of biotic evolution, SMHT, a sulfonium compound, may have fulfilled the present day methyl donor function of S-adenosylmethionine. Existing homologies between methionyl-tRNA synthetase and S-adenosylmethionine synthetase indicate evolutionary relatedness of the two proteins.