Biology Reference
In-Depth Information
CHAPTER THREE
A Mechanistic Comparison of the
Varkud Satellite and Hairpin
Ribozymes
Timothy J. Wilson, David M.J. Lilley
Cancer Research UK Nucleic Acid Structure Research Group, The University of Dundee, Dundee, United
Kingdom
Contents
1.
Introduction
94
2. The Hairpin and VS Ribozymes
95
2.1 The secondary structures of the hairpin and VS ribozymes—the role of helical
junctions
96
2.2 Structure and dynamics of the hairpin ribozyme
97
2.3 Structure and dynamics of the VS ribozyme
99
2.4 Identification of the active site of the VS ribozyme
101
2.5 A new crystal structure of the VS ribozyme
103
2.6 The catalytic mechanism of the VS ribozyme
104
2.7 Cleavage and ligation reactions in the hairpin ribozyme—the internal
equilibrium
109
2.8 Candidate catalytic components in the hairpin ribozyme
110
2.9 The catalytic mechanism of the hairpin ribozyme
is it same as that
of the VS ribozyme?
111
3. General Themes
114
Acknowledgments
116
References
116
Abstract
The hairpin and Varkud satellite ribozymes are two members of the class of nucleolytic
ribozymes that catalyze cleavage and ligation reactions at a specific site. Cleavage occurs
by a transesterification reaction whereby the 2 0 -O attacks the adjacent phosphorus with
departure of the 5 0 -O to leave a 2 0 ,3 0 -cyclic phosphate. The structures of both ribozymes
are now known. Although the sequences and structures of these ribozymes are gener-
ally unrelated, the topological organization and the arrangement of the active sites are
the same for both. Both mechanistic and structural data indicate that the ribozymes
employ general acid-base catalysis to accelerate the transesterification reactions, using
guanine and adenine nucleobases as the general base and acid, respectively, in the
 
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