Mechanistic aspects of enzymatic catalysis: Lessons from comparison of RNA and protein enzymes

A classic approach in biology, both organismal and cellular, is to compare morphologies in order to glean structural and functional commonalities. The comparative approach has also proven valuable on a molecular level. For example, phylogenetic comparisons of RNA sequences have led to determination of conserved secondary and even tertiary structures, and comparisons of protein structures have led to classifications of families of protein folds. Here we take this approach in a mechanistic direction, comparing protein and RNA enzymes. The aim of comparing RNA and protein enzymes is to learn about fundamental physical and chemical principles of biological catalysis. The more recently discovered RNA enzymes, or ribozymes, provide a distinct perspective on longstanding questions of biological catalysis. The differences described in this review have taught us about the aspects of RNA and proteins that are distinct, whereas the common features have helped us to understand the aspects that are fundamental to biological catalysis. This has allowed the framework that was put forth by Jencks for protein catalysts over 20 years ago (1) to be extended to RNA enzymes, generalized, and strengthened.