Proton Transfer in Ribozyme Catalysis

This chapter provides an overview of recent progress in understanding proton transfer in RNA enzymes. It was over 10 years ago that the previous book by the same editors was published. In that volume, there was no chapter on proton transfer. Indeed, it was unclear whether proton transfer made important contributions to RNA catalysis. Many things have changed in the last decade. Most importantly, RNA structural biology has flourished. There are now high-resolution structures of many RNA enzymes, both large and small, and many features of these structures have been tested and confirmed in biochemical experiments. Relevant to this chapter, ribozyme structures have provided inspiration for probing and, in some instances, demonstrating roles for proton transfer in RNA catalysis. In this chapter, I provide an overview of the evolution of proton transfer research in RNA enzymes, largely from an historical perspective. The chapter begins with a definition of proton transfer and consideration of why proton transfer is important to the mechanisms of most enzyme-catalyzed reactions. A brief overview of proton transfer in protein reactions is provided, including the usage of amino acids other than histidine, and the importance of pKa shifting. Next, the chapter focuses on RNA enzymes. The extent to which the four natural nucleobases can directly partake in proton transfer is assessed. The benefit that large and small ribozymes might derive from proton transfer is considered from the point of view of the uncatalyzed reaction, as are possible quantitative contributions to catalysis. The chapter concludes with case studies