Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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5' Untranslated Regions
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Base Pairing
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Base Sequence
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Binding Sites
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Catalysis
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Crystallization
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Crystallography, X-Ray
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Enzyme Activation
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology
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Glucosamine / analogs & derivatives*
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Glucosamine / metabolism
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Glucose-6-Phosphate / analogs & derivatives*
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Glucose-6-Phosphate / metabolism
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Glucose-6-Phosphate / pharmacology
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Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / genetics*
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Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / metabolism
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Hydrogen Bonding
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Ligands
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Molecular Sequence Data
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Nucleic Acid Conformation
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RNA, Catalytic / chemistry*
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RNA, Catalytic / metabolism*
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Thermoanaerobacter / enzymology
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Thermoanaerobacter / genetics*
Substances
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5' Untranslated Regions
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Enzyme Inhibitors
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Ligands
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RNA, Catalytic
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glucosamine 6-phosphate
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Glucose-6-Phosphate
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Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
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Glucosamine
Associated data
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PDB/2GCS
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PDB/2GCV
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PDB/2H0S
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PDB/2H0W
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PDB/2H0X
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PDB/2H0Z
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PDB/2HO6
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PDB/2HO7