MECHANISM FOR ALLOSTERIC INHIBITION OF AN ATP-SENSITIVE RIBOZYME

We report the structural basis for the modulation of an ATP-sensitive ribozyme that was engineered by modular rational design. This alloster ic 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 f unctions as an allosteric ribozyme that is inhibited in the presence o f ATP. The aptamer domain remains conformationally heterogeneous in th e absence of ATP, but folds into a distinct structure upon ligand bind ing. This ATP-induced conformational change causes a reduction in cata lytic activity of the adjacent ribozyme domain due to steric interfere nce between the aptamer and ribozyme tertiary structures. This mechani sm 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.