Modeling of a possible conformational change associated with the catalytic mechanism in the hammerhead ribozyme

Robert F. Setlik, Masayuki Shibata, Ramaswamy H. Sarma, Mukti H. Sarma, A. Latif Kazim, Rick L. Omstein, Thomas B. Tomasi, Robert Rein

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12 Scopus citations


Here we describe a possible model of the cleavage mechanism in the hammerhead ribozyme. In this model, the 2’ hydroxyl of Cl7 is moved into an appropriate orientation for an in-line attack on the Gl.l phosphate through a change in its sugar pucker from C3’ endo to C2’ endo. This conformational change in the active site is caused by a change in the uridine turn placing the N2 and N3 atoms of G5 of the conserved core in hydrogen bonding geometry with the N3 and N2 atoms on the conserved G16.2 residue. The observed conformational change in the uridine turn suggests an explanation for the conservation of G5. In the crystal structure of H.M. Pley et al., Nature 372, 68-74 (1994), G5 is situated 5.3Å away from G16.2. However, the uridine turn is sufficiently flexible to allow this conformational change with relatively modest changes in the backbone torsion angles (average change of 14.2°). Two magnesium ions were modeled into the active site with positions analogous to those described in the functionally similar Klenow fragment 3’-5’ exonuclease (L.S. Beese and T.A. Steitz, EMBO J. 10, 25-33 (1991)), the Group I intron (T.A. Steitz and J.A. Steitz, P.N.A.S. U.S.A. 90, 6498-6502 (1993); R.F. Setlik et al., J. Biomol. Str. Dyn. 10, 945-972 (1993)) and other phosphotransferases. Comparison of this model with one in which the uridine turn conformation was not changed showed that although the changes in the C17 sugar pucker could be modeled, insufficient space existed for the magnesium ions in the active site.

Original languageEnglish (US)
Pages (from-to)515-522
Number of pages8
JournalJournal of Biomolecular Structure and Dynamics
Issue number3
StatePublished - Dec 1995
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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