GlmS glucosamine-6-phosphate activated ribozyme
RNA family
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Through Metabolite, Catalysis and Nucleic acid double helix
Structure
The structure of the glmS ribozyme was first determined by X-ray crystallography in 2006. The tertiary structure of this RNA is characterized by three coaxial stacked helices, packed side by side. The ribozyme core contains a double pseudoknotted structure, which places the central helix P2.1 such that the scissile phosphate is nestled by the major groove. The major groove of the adjacent helix P2.2 is involved in metabolite binding and the scissile phosphate is attached to the 5' end of the helix. The roof of the active site is characterized by conserved base triples, which connect P2.1 and P2.2 stacks and the floor consists of a non-conserved G-U pair, which are splayed apart. By examining superimposition of ribozyme structures in a pre-cleavage state, metabolite bound state and post cleavage state, it was determined there is no gross conformational change upon metabolite binding, which is indicative of a preorganized active site that depends on GlcN6P as a cofactor, not an allosteric activator. The cofactor is bound in a solvent-accessible pocket and the structure suggests that the amine group of GlcN6P is involved in the catalytic process.
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Cleavage Requirements
Although glmS ribozyme performs self-cleavage upon binding GlcN6P, the glmS ribozyme active site does not undergo conformational change upon binding GlcN6P. Instead, the active site is pre-formed and glmS ribozyme activity is triggered by the introduction of a functional group on GlcN6P that is necessary for catalysis. As mentioned above, the amine group on GlcN6P is thought to be the catalytically involved functional group, which is supported by studies that evaluated glmS ribozyme activity using different ligands, under physiologic conditions. For example, these experiments found that incubation with Glc6P (no amine group) inhibits glmS self-cleavage while incubation with GlcN (available amine group) stimulates cleavage, though not to the extent that GlcN6P does. These and other findings indicate that the glmS ribozyme is a unique class of ribozyme, and that its discovery is further evidence of the catalytic capacity of RNA.