Abstract :
The glmS ribozyme is the first known example of a natural ribozyme that hasevolved to require binding of an exogenous small molecule for activity. In Gram-positivebacteria, this RNA domain is part of the messenger RNA (mRNA) encoding the essentialenzyme that synthesizes glucosamine-6-phosphate (GlcN6P). When present at physiologicconcentration, this small molecule binds to the glmS ribozyme and uncovers a latent self-cleavage activity that ultimately leads to degradation of the mRNA. Biochemical and structuralstudies reveal that the RNA adopts a rigid fold stabilized by three pseudoknots and thepacking of a peripheral domain against the ribozyme core. GlcN6P binding to this pre-organized RNA does not induce conformational changes ; rather, the small molecule functionsas a coenzyme, providing a catalytically essential amine group to the active site. The ribozymeis not a passive player, however. Active site functional groups are essential for catalysis, even inthe presence of GlcN6P. In addition to being a superb experimental system with which toanalyze how RNA catalysts can exploit small molecule coenzymes to broaden their chemicalversatility, the presence of the glmS ribozyme in numerous pathogenic bacteria make this RNAan attractive target for the development of new antibiotics and antibacterial strategies
