Biological catalysis: Lessons from the comparison of RNA and protein enzymes

RNA enzymes, or ribozymes, provide a distinct perspective on long-standing queslion.s of biological catalysis. The differences observed between RNA and protein enzymes have taught us about aspects of RNA and proteins that are distinct, whereas the common features have helped us understand the aspects that are fundamental to biological catalysis. RNA enzymes, like protein en /vines, are able to use binding interactions away from the site of chemical transformation to facilitate that transformation by positioning substrates with respect to catalytic functional groups and by inducing electrostatic ground state destabilization. These observations allow the concept of 'intrinsic bind ing energy', put forth by Jencks, to be extended to RNA enzymes, generalized and strengthened. In addition, RNA enzymes appear to be highly amenable to energetic dissection of function. These analyses have general implications for understanding the role of binding interactions in catalysis and for understanding the evolution of catalysts. Results with the RNA enzymes will be placed in a conceptual framework for enzymatic catalysis. This framework will further be used to analyze catalytic contributions from enzymatic groups that interact at the site of bond transformation. It is suggested that the enzymatic environment can enhance the ability of hydrogen bonds to preferentially stabilize the- transition stale, thereby providing rate enhancement relative to the corresponding solution reaction.