Enzyme-catalyzed methyl transfers to thiols: the role of zinc

Zinc has been identified as a cofactor in a growing number of proteins that utilize thiols as nucleophiles, including proteins that catalyze the transfer of methyl groups to thiols. The latter category includes the Ada protein involved in the response of E. coli to DNA alkylation, cobalamin-independent and cobalamin-dependent methionine synthase, and enzymes involved in the formation of methylcoenzyme M in methanogenesis. Farnesyl-protein transferase and geranylgeranyl-protein transferase also contain zinc and an X-ray structure of farnesyl-protein transferase has recently been determined. Within the past year, studies on the role of zinc in these proteins and in model compounds have shown that the thiol substrates are coordinated to the zinc as thiolates, suggesting a role for zinc in maintenance of thiol reactivity at neutral pH.