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Atomic-resolution structure of a ribozyme yields insights into RNA catalysis and the origins of life

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Using the technique of macromolecular x-ray crystallography, Martick and Scott were able to obtain a three-dimensional picture of the spatial arrangement of the several thousand atoms that comprise the ribozyme, known as the hammerhead ribozyme. The resulting color-coded structure was recently featured on the cover of the abstract book for the annual meeting of the RNA Society held in Seattle in early June.

"The structure illustrates unambiguously how functional groups of the RNA mediate acid-base chemical catalysis, permitting us to suggest that acid-base chemistry is so fundamental to enzyme catalysis that it predates the origin of protein enzymes," Scott said.

For Scott, these results are the culmination of 19 years of research on the structure of the hammerhead ribozyme. He started work on the project as a graduate student at UC Berkeley in 1987, a few months after the ribozyme was discovered. Later, as a postdoctoral researcher at the MRC Laboratory of Molecular Biology in Cambridge, England, he achieved his first breakthrough.

Scott subsequently built an internationally-recognized research team at UCSC that has performed static and time-resolved experiments resulting in the first crystallographic time-lapse "movie" of ribozyme catalysis. His group has also elucidated structures of other RNAs, including the recent structure of a highly conserved motif from the SARS virus genome.

Scott's structural observations of the hammerhead ribozyme, however, could not explain a growing number of biochemical experimental results. The hammerhead ribozyme has been the subject of intensive investigations by researchers around the world, and Scott found his most cherished accomplishments called into question.

"In 2002, I had two very lucky breaks," he said. "The first was that I learned of a new form of this ribozyme that was 1,000 times faster than the most widely studied form. T
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Contact: Tim Stephens
stephens@ucsc.edu
831-459-2495
University of California - Santa Cruz
20-Jul-2006


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