An equivalent metal ion in one- and two-metal-ion catalysis

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Abstract
Most known nucleotidyl-transfer enzymes use two metal ions for catalysis, but some enzymes use only one divalent cation in their active sites. A comparative analysis of previously available structural data reveals that the one-metal-ion enzymes use a similar mechanism to coordinate their single metal ion, which corresponds, functionally and structurally, to metal ion B in the two-metal-ion enzymes. Nucleotidyl-transfer enzymes, which synthesize, degrade and rearrange DNA and RNA, often depend on metal ions for catalysis. All DNA and RNA polymerases, MutH-like or RNase H–like nucleases and recombinases, and group I introns seem to require two divalent cations to form a complete active site. The two-metal-ion mechanism has been proposed to orient the substrate, facilitate acid-base catalysis and allow catalytic specificity to exceed substrate binding specificity attributable to the stringent metal-ion (Mg2+ in particular) coordination. Not all nucleotidyl-transfer enzymes use two metal ions for catalysis, however. The ββα-Me and HUH nucleases depend on a single metal ion in the active site for the catalysis. All of these one- and two metal ion–dependent enzymes generate 5′-phosphate and 3′-OH products. Structural and mechanistic comparisons show that these seemingly unrelated nucleotidyl-transferases share a functionally equivalent metal ion.