Structural basis of glmS ribozyme activation by glucosamine-6-phosphate.
The glmS ribozyme is the only natural catalytic RNA known to require a small-molecule activator for catalysis. This catalytic RNA functions as a riboswitch, with activator-dependent RNA cleavage regulating glmS messenger RNA expression. We report crystal structures of the glmS ribozyme in precleavage states that are unliganded or bound to the competitive inhibitor glucose-6-phosphate and in the postcleavage state. All structures superimpose closely, revealing a remarkably rigid RNA that contains a preformed active and coenzyme-binding site. Unlike other riboswitches, the glmS ribozyme binds its activator in an open, solvent-accessible pocket. Our structures suggest that the amine group of the glmS ribozyme-bound coenzyme performs general acid-base and electrostatic catalysis.
Klein
Daniel J
DJ
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109-1024, USA.
Ferré-D'Amaré
Adrian R
AR
D020121:5' Untranslated Regions; D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D002384:Catalysis; D003460:Crystallization; D018360:Crystallography, X-Ray; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000235:genetics* / Q000378:metabolism; D006860:Hydrogen Bonding; D008024:Ligands; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016337:RNA, Catalytic / Q000737:chemistry* / Q000378:metabolism*; D046968:Thermoanaerobacter / Q000201:enzymology / Q000235:genetics*
D020121:5' Untranslated Regions; D004791:Enzyme Inhibitors; D008024:Ligands; D016337:RNA, Catalytic; C001293:glucosamine 6-phosphate; D019298:Glucose-6-Phosphate; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing); D005944:Glucosamine