In the six months since this laboratory was established, we have made important progress in understanding the molecular basis of action of the glmS ribozyme-riboswitch. This is a gene-regulatory catalytic RNA that controls the synthesis of an essential precursor for the cell wall of Gram-positive bacteria. We had previously established that this RNA recruits a small molecule metabolite to carry out catalytic degradation of a mRNA. Our new studies demonstrate that the RNA active site not only binds to this small molecule, but actively perturbs its chemical properties to enhance catalysis. This is the first demonstration that RNA active sites are capable of such sophistication. This work is part of our effort to target the glmS ribozyme-riboswitch with artificial compounds that may provide leads for the development of new antibiotics. In addition, this RNA may also serve as a starting point for the development of new technologies that enable small-molecule directed RNA cleavage in vivo. Work in the development of new enabling technologies also included the structural characterization of a spectroscopic probe that allows accurate characterization of nucleic acid structure and dynamics employing EPR and fluorescence spectroscopies.
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