4FEN: Crystal Structure of the A24u/u25a/a46g Mutant Xpt-pbux Guanine Riboswitch Aptamer Domain in Complex With Hypoxanthine

Direct sensing of intracellular metabolite concentrations by riboswitch RNAs provides an economical and rapid means to maintain metabolic homeostasis. Since many organisms employ the same class of riboswitch to control different genes or transcription units, it is likely that functional variation exists in riboswitches such that activity is tuned to meet cellular needs. Using a bioinformatic approach, we have identified a region of the purine riboswitch aptamer domain that displays conservation patterns linked to riboswitch activity. Aptamer domain compositions within this region can be divided into nine classes that display a spectrum of activities. Naturally occurring compositions in this region favor rapid association rate constants and slow dissociation rate constants for ligand binding. Using X-ray crystallography and chemical probing, we demonstrate that both the free and bound states are influenced by the composition of this region and that modest sequence alterations have a dramatic impact on activity. The introduction of non-natural compositions result in the inability to regulate gene expression in vivo, suggesting that aptamer domain activity is highly plastic and thus readily tunable to meet cellular needs.
PDB ID: 4FENDownload
MMDB ID: 107945
PDB Deposition Date: 2012/5/30
Updated in MMDB: 2013/05 
Experimental Method:
x-ray diffraction
Resolution: 1.35  Å
Source Organism:
Biological Unit for 4FEN: monomeric; determined by author and by software (PISA)
Molecular Components in 4FEN
Label Count Molecule
Nucleotide(1 molecule)
A24u/u25a/a46g Mutant of the B. Subtilis Xpt-pbux Guanine Riboswitch Aptamer Domain
Molecule annotation
Chemicals (9 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB