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Modeling of a possible conformational change associated with the catalytic mechanism in the hammerhead ribozymeHere we describe a possible model of the cleavage mechanism in the hammerhead ribozyme. In this model, the 2' hydroxyl of C17 is moved into an appropriate orientation for an in-line attack on the G1.1 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 5.3A 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 degrees). 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.
Document ID
20040173328
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Setlik, R. F.
(Roswell Park Cancer Institute Buffalo, New York 14263, United States)
Shibata, M.
Sarma, R. H.
Sarma, M. H.
Kazim, A. L.
Ornstein, R. L.
Tomasi, T. B.
Rein, R.
Date Acquired
August 22, 2013
Publication Date
December 1, 1995
Publication Information
Publication: Journal of biomolecular structure & dynamics
Volume: 13
Issue: 3
ISSN: 0739-1102
Subject Category
Exobiology
Funding Number(s)
CONTRACT_GRANT: GM 29789-20
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Exobiology

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