For many years, enzymatic activity was thought to be exclusively attributable to proteins. However, it was discovered that some RNAs, called ribozymes, can also direct enzymatic reactions, without the intervention of proteins. In recent years, many examples of ribozymes have been identified, and it is now commonly accepted that while most enzymes are proteins, there are a significant number of ribozymes in the biological world.

[6 pts] Think about the sorts of secondary structures and tertiary interactions that allow proteins to fold into specific three dimensional structures and enable them to function as enzymes. Using similar structural considerations and proper terminology for nucleic acid structure, explain why RNA makes a good catalytic molecule and conversely why DNA does not (Refer to Karp Fig. 2.48 and Fig. 11.43 for examples of RNA structure, and 10.10ac for DNA). Limit your answer to 3 sentences.

Different proteins have a tertiary (or quaternary) structure that can generate an active site containing reactive amino acids for enzyme activity and that is flexible enough to allow induced fit when the substrate binds. RNA is a good catalytic molecule also because it can partially base pair with itself to form specific secondary/tertiary structures which allow substrate recognition, is flexible, and has a 2' OH that can be reactive (as well as the 3' OH). DNA secondary structure is typically a regularly shaped double helix, more rigid with all bases already paired, and has no 2' OH.

II. [4 pts] The majority of ribozymes act on nucleic acids, often cleaving phosphodiester linkages at specific sequences in RNA or possibly even DNA (i.e. ribonucleases or deoxyribonucleases). Why is it not surprising, again in structural terms, that an enzyme composed of RNA would evolve to recognize and cleave itself or other RNA or DNA? (Hint:: Enzymes bind to their substrates by recognizing unique chemical or structural features of that substrate). Limit your answer to 2 sentences.

RNA structures have open loops for base pairing which allows them to recognize a particular target sequence in an RNA or a small opened portion of a DNA substrate where the bases are available. RNA can then cleave specific locations in the sugar-phosphate backbone.