Mechanistic studies of proton transfer in ribozyme self-cleavage

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With this award, the Chemistry of Life Processes program is supporting the research of Professor Bevilacqua of Pennsylvania State University to examine proton transfer in a small, non-metalloribozyme. It is presently unclear how the initial step in this reaction--attack of a 2'hydroxyl on an adjacent phosphate--is catalyzed. Two limiting models of participation of an anionic guanine and of a solvent-resident species will be examined. Goals of this research are to identify the general (or specific) base in the reaction, determine its pKa, examine the driving forces for pKa shifting, and establish the base's contributions to proton transfer in the chemical step. Complementary experiments on model systems will be conducted in an effort to identify driving forces for pKa shifting.The Broader Impacts of this project are three-fold. First, several undergraduates will participate in the research. They will measure driving forces for pKa shifting in nucleotides and oligonucleotides and be broadly trained. Second, the PI will help develop a departmental-wide program in undergraduate thesis research. Undergraduates conducting original research will write and orally defend a research topic. This process will involve several semesters of research and one summer. Last, the results of this research project will be broadly disseminated through both publication and programs/podcasts available to the public.