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Originally published in Science Express on 10 October 2002
Science 15 November 2002:
Vol. 298. no. 5597, pp. 1421 - 1424
DOI: 10.1126/science.1076093
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Reports

Transition State Stabilization by a Catalytic RNA

Peter B. Rupert,1 Archna P. Massey,2 Snorri Th. Sigurdsson,2 Adrian R. Ferré-D'Amaré1*

The hairpin ribozyme catalyzes sequence-specific cleavage of RNA through transesterification of the scissile phosphate. Vanadate has previously been used as a transition state mimic of protein enzymes that catalyze the same reaction. Comparison of the 2.2 angstrom resolution structure of a vanadate-hairpin ribozyme complex with structures of precursor and product complexes reveals a rigid active site that makes more hydrogen bonds to the transition state than to the precursor or product. Because of the paucity of RNA functional groups capable of general acid-base or electrostatic catalysis, transition state stabilization is likely to be an important catalytic strategy for ribozymes.

1 Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109-1024, USA.
2 Department of Chemistry, University of Washington, Box 351700, Seattle, WA 98195-1700, USA.
*   To whom correspondence should be addressed. E-mail: aferre{at}fhcrc.org

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