The glmS ribozyme: use of a small molecule coenzyme by a gene-regulatory RNA.
The glmS ribozyme is the first known example of a natural ribozyme that has evolved to require binding of an exogenous small molecule for activity. In Gram-positive bacteria, this RNA domain is part of the messenger RNA (mRNA) encoding the essential enzyme that synthesizes glucosamine-6-phosphate (GlcN6P). When present at physiologic concentration, 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 structural studies reveal that the RNA adopts a rigid fold stabilized by three pseudoknots and the packing of a peripheral domain against the ribozyme core. GlcN6P binding to this pre-organized RNA does not induce conformational changes; rather, the small molecule functions as a coenzyme, providing a catalytically essential amine group to the active site. The ribozyme is not a passive player, however. Active site functional groups are essential for catalysis, even in the presence of GlcN6P. In addition to being a superb experimental system with which to analyze how RNA catalysts can exploit small molecule coenzymes to broaden their chemical versatility, the presence of the glmS ribozyme in numerous pathogenic bacteria make this RNA an attractive target for the development of new antibiotics and antibacterial strategies.
Ferré-D'Amaré
Adrian R
AR
Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109-1024, USA. aferre@fhcrc.org
D001426:Bacterial Proteins / Q000378:metabolism; D001483:Base Sequence; D055162:Biocatalysis; D003067:Coenzymes / Q000737:chemistry / Q000378:metabolism*; D005944:Glucosamine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D016337:RNA, Catalytic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D058928:Riboswitch / Q000235:genetics*
D001426:Bacterial Proteins; D003067:Coenzymes; D016337:RNA, Catalytic; D058928:Riboswitch; C001293:glucosamine 6-phosphate; D019298:Glucose-6-Phosphate; D005944:Glucosamine
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