title: Carba-sugars activate the glmS-riboswitch of Staphylococcus aureus.
abstract: The glmS-riboswitch is unique among riboswitch families as it represents a metabolite-dependent ribozyme that undergoes self-cleavage upon recognition of glucosamin-6-phosphate. The glmS-riboswitch is located in the 5'-untranslated region of bacterial genes involved in cell wall biosynthesis. Therefore, this riboswitch represents a promising target for developing new antibiotics. We describe the metabolite-dependent glmS-riboswitch of pathologically relevant and vancomycin-resistant Staphylococcus aureus and the discovery and synthesis of a carba-sugar with potency similar to that of the native metabolite glucosamine-6-phosphate in modulating riboswitch activity. This compound represents a valuable lead structure for the development of antibiotics with a novel mode of action.
authors.forename: Christina E
authors.initials: CE
authors.lastname: Lünse
authors.forename: Magnus S
authors.initials: MS
authors.lastname: Schmidt
authors.forename: Valentin
authors.initials: V
authors.lastname: Wittmann
authors.forename: Günter
authors.initials: G
authors.lastname: Mayer
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D054329:Carbasugars / Q000737:chemistry* / Q000378:metabolism*; D005944:Glucosamine / Q000031:analogs & derivatives / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D016337:RNA, Catalytic / Q000502:physiology*; D058928:Riboswitch / Q000502:physiology*; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*; D020713:Vancomycin Resistance / Q000235:genetics; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
chemical_list: D001426:Bacterial Proteins; D054329:Carbasugars; D005944:Glucosamine; D019298:Glucose-6-Phosphate; D008274:Magnesium; D016337:RNA, Catalytic; D058928:Riboswitch; C001293:glucosamine 6-phosphate; C000731191:component S, glutamate mutase protein, Bacteria; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)