Professor — Bioinorganic Chemistry, Biophysical Chemistry & Chemical Biology
B.A., University of Chicago, 1983. PhD, University of California-Berkeley, 1990 (Mel Klein and Ken Sauer). Postdoctoral: Northwestern University (Brian Hoffman). Assistant (1995-01) and Associate (2001-05) Professor of Chemistry, Texas A&M University. Honors and Awards: NIH Postdoctoral fellow, 1991-94; NSF CAREER awardee, 1997; Research Corporation Cottrell Scholar, 1998; Center for Teaching Excellence Montague Scholar,1999; AFS College of Science Teaching Award, 2000. University of Oregon Fund for Faculty Members Excellence Award, 2008. American Association for the Advancement of Science Fellow, 2010. At UO since 2006.
RNA is a truly unique biopolymer that displays a rich array of cellular functions, some of which are still being uncovered. RNA structure itself is complex and dynamic, and can be profoundly influenced by ionic conditions. One long-term objective of our research program is to directly measure cation-RNA interactions and understand their importance in function. Catalytic RNAs, or ribozymes, provide model systems for these studies. Since their discovery approximately two decades ago, the mechanisms by which RNA catalyzes reactions have been an area of intense investigation. Biological ribozymes catalyze phosphoryl transfer reactions in RNA processing and splicing events. A growing body of evidence indicates that the aminoacyl transferase activity of the ribosome also is catalyzed in an RNA-formed active site. Cations influence activity in these systems by mechanisms that are not entirely understood, but range from general electrostatic effects to population of very specific ‘sites’ created by the folded RNA. Our current projects include detailed studies of ribozymes such as the hammerhead motif derived from the genomes of plant viroids and other organisms. We are also initiating an investigation of the interactions of metal-based therapeutics, such as the anticancer compound cisplatin, with structured RNAs.
In the active sites of metalloenzymes, the properties of metal ions are highly tuned by their protein environments. In order to understand the importance of different ‘spheres of influence’ that the protein exerts on the metal ion, we are designing and investigating small peptides based on the metal-binding cavities of naturally-occurring enzymes. The active sites of blue copper proteins and of mononuclear Fe and Co-containing enzymes are current targets using both rational and combinatorial methods to create appropriate peptide models.
These studies require spectroscopic techniques that examine global structure as well as provide a window of observation around the metal ion. EPR, NMR, fluorescence, and other spectroscopic methods are used in these projects. SDSL (site-directed spin labeling) allows tracking of RNA structure by monitoring changes in local dynamics and interprobe distances. ENDOR (electron nuclear double resonance) spectroscopy is a double resonance technique that detects only nuclei that are coupled to a paramagnetic metal ion. When combined, these methods provide unique information about global structure and local environments in the active sites of metalloproteins and ribozymes.
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