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30 August 2006

  The Elusive Active Fold of a Catalytic RNA
 
 

Genes, which are made of nucleic acids (DNA or RNA) contain the instructions for how to make proteins, but still enzymes made of proteins are needed to replGenes, which are made of nucleic acids (DNA or RNA) contain the instructions for how to make proteins, but still enzymes made of proteins are needed to replicate the genes. This paradox was addressed ~20 years ago with the realization that some kinds of RNA can act as enzymes. These RNA enzymes, or ribozymes, are accordingly made of the genetic RNA material, but they act as chemical catalysts. This means that ribozymes would have enabled the first self-replicating molecules, also made of RNA, to copy themselves.

Scientists at the University of California-Santa Cruz came to Stanford Synchrotron Radiation Laboratory and the Advanced Light Source to use macromolecular crystallography beam line facilities to determine the three-dimensional structure of a full-length hammerhead ribozyme. The structure shows how the specific spatial arrangement of functional groups of the RNA allows them to mediate acid-base chemical catalysis. The researchers conclude that it appears these aspects of acid-base catalysis are so fundamental that they might be considered universal principles of macromolecular enzymology (both for proteins and RNAs).

The new findings are described by graduate student Monika Martick and her advisor, Professor William Scott, in the July 27 issue of the journal Cell.

Many academic and industrial laboratories are engineering ribozymes for potential use in fighting infectious and chronic diseases.

To learn more about this research see the full scientific highlight at:
http://www-ssrl.slac.stanford.edu/ research/highlights_archive/ribozyme.html

Monika Martick and William G. Scott, Tertiary Contacts Distant from the Active Site Prime a Ribozyme for Catalysis Cell 126: 309-320 (2006).