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

Nature Structural & Molecular Biology volume 15, pages 1228–1231 (2008)Cite this article

Abstract

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.

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Figure 1: A diagram of two-metal-ion catalysis by RNase H.
Figure 2: Examples of one metal ion–dependent nucleases.
Figure 3: Comparison of the active site of RNase H and TraI in stereo view.

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Acknowledgements

I thank C. Biertümpfel, C. Larkin and M. Nowotny for stimulating discussion, and B. Craigie, F. Dyda, D. Leahy and H. Yuan for critical reading of the manuscript. This research was supported by the Intramural Research Program of the US National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.

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  1. Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, Building 5, Room B1-03, Bethesda, 20892, Maryland, USA

    Wei Yang

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Correspondence to Wei Yang.

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Yang, W. An equivalent metal ion in one- and two-metal-ion catalysis. Nat Struct Mol Biol 15, 1228–1231 (2008). https://doi.org/10.1038/nsmb.1502

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