Structural investigation of the GlmS ribozyme bound to Its catalytic cofactor.
The GlmS riboswitch is located in the 5'-untranslated region of the gene encoding glucosamine-6-phosphate (GlcN6P) synthetase. The GlmS riboswitch is a ribozyme with activity triggered by binding of the metabolite GlcN6P. Presented here is the structure of the GlmS ribozyme (2.5 A resolution) with GlcN6P bound in the active site. The GlmS ribozyme adopts a compact double pseudoknot tertiary structure, with two closely packed helical stacks. Recognition of GlcN6P is achieved through coordination of the phosphate moiety by two hydrated magnesium ions as well as specific nucleobase contacts to the GlcN6P sugar ring. Comparison of this activator bound and the previously published apoenzyme complex supports a model in which GlcN6P does not induce a conformational change in the RNA, as is typical of other riboswitches, but instead functions as a catalytic cofactor for the reaction. This demonstrates that RNA, like protein enzymes, can employ the chemical diversity of small molecules to promote catalytic activity.
Cochrane
Jesse C
JC
Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Avenue, New Haven, CT 06520, USA.
Lipchock
Sarah V
SV
Strobel
Scott A
SA
D020121:5' Untranslated Regions; D001408:Bacillus anthracis / Q000201:enzymology; D001665:Binding Sites; D018360:Crystallography, X-Ray; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000737:chemistry*; D008274:Magnesium; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D010710:Phosphates; D011485:Protein Binding; D016337:RNA, Catalytic / Q000737:chemistry*
D020121:5' Untranslated Regions; D010710:Phosphates; D016337:RNA, Catalytic; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing); D008274:Magnesium