Nucleic Acids Research, Vol 26, Issue 18 4214-4221, Copyright © 1998 by Oxford University Press
J Tang and RR Breaker
We report the structural basis for the modulation of an ATP-sensitive
ribozyme that was engineered by modular rational design. This allosteric
ribozyme is composed of two independently functioning domains, one a
receptor for ATP and the other a self-cleaving ribozyme. When fused in the
appropriate fashion, the conjoined aptamer-ribozyme construct functions as
an allosteric ribozyme that is inhibited in the presence of ATP. The
aptamer domain remains conformationally heterogeneous in the absence of
ATP, but folds into a distinct structure upon ligand binding. This
ATP-induced conformational change causes a reduction in catalytic activity
of the adjacent ribozyme domain due to steric interference between the
aptamer and ribozyme tertiary structures. This mechanism for structural and
functional modulation of nucleic acids is one of several possible
mechanisms by which the function of ribozymes could be specifically
controlled by small effector molecules.
ARTICLES
Mechanism for allosteric inhibition of an ATP-sensitive ribozyme
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA.
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