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Figure 3.10 Schematic of the secondary structures of the hairpin and VS ribozymes
drawn to highlight the equivalence of the two active sites. 89 The secondary structures
are arranged to bring the interacting internal loops side by side, showing the A and
B loops for the hairpin ribozyme (shown left) and the substrate and A730 loops for
the VS ribozyme (shown right). Strand polarities in the active sites (boxed) are identical.
Note that the key components including the scissile phosphate (encircled P) and the
critical adenine (A) and guanine (G) nucleobases are equivalently positioned in each
ribozyme. Although the overall structures of the two ribozyme have little in common,
the two active sites are topologically the same.
two internal loops. In both cases, an active guanine lies on the opposing
strand of the internal loop harboring the scissile phosphate and is implicated
in activation of the 2 0 -OH nucleophile, while an active adenine is provided
by the second loop and probably interacts with O5 0 . 22,34 The topologies of
the two ribozymes appear identical when the polarity of the strands is con-
sidered ( Fig. 3.10 ), and the structures of the two active sites are very similar.
So do these ribozymes share a common mechanism using general acid-base
catalysis?
From the outset, it was recognized that G8 and A38 of the hairpin ribo-
zyme might participate in general acid-base catalysis. 34,38,68,80 This hypoth-
esis was expounded with great clarity by Bevilacqua, 61 who showed that
the observed pH dependence of the reaction was consistent with general
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