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Science 9 October 1998:
Vol. 282. no. 5387, pp. 259 - 264
DOI: 10.1126/science.282.5387.259
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Research Articles

A Preorganized Active Site in the Crystal Structure of the Tetrahymena Ribozyme

Barbara L. Golden, * Anne R. Gooding, Elaine R. Podell, Thomas R. Cech *

Group I introns possess a single active site that catalyzes the two sequential reactions of self-splicing. An RNA comprising the two domains of the Tetrahymena thermophila group I intron catalytic core retains activity, and the 5.0 angstrom crystal structure of this 247-nucleotide ribozyme is now described. Close packing of the two domains forms a shallow cleft capable of binding the short helix that contains the 5' splice site. The helix that provides the binding site for the guanosine substrate deviates significantly from A-form geometry, providing a tight binding pocket. The binding pockets for both the 5' splice site helix and guanosine are formed and oriented in the absence of these substrates. Thus, this large ribozyme is largely preorganized for catalysis, much like a globular protein enzyme.

Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309-0215, USA.
*   To whom correspondence should be addressed. E-mail: bgolden{at}petunia.colorado.edu (B.L.G.); Thomas.Cech{at}colorado.edu (T.R.C.).

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