3NPQ: Structure Of The S-Adenosylhomocysteine Riboswitch At 2.18 A

S-adenosyl-(L)-homocysteine (SAH) riboswitches are regulatory elements found in bacterial mRNAs that up-regulate genes involved in the S-adenosyl-(L)-methionine (SAM) regeneration cycle. To understand the structural basis of SAH-dependent regulation by RNA, we have solved the structure of its metabolite-binding domain in complex with SAH. This structure reveals an unusual pseudoknot topology that creates a shallow groove on the surface of the RNA that binds SAH primarily through interactions with the adenine ring and methionine main chain atoms and discriminates against SAM through a steric mechanism. Chemical probing and calorimetric analysis indicate that the unliganded RNA can access bound-like conformations that are significantly stabilized by SAH to direct folding of the downstream regulatory switch. Strikingly, we find that metabolites bearing an adenine ring, including ATP, bind this aptamer with sufficiently high affinity such that normal intracellular concentrations of these compounds may influence regulation of the riboswitch.
PDB ID: 3NPQDownload
MMDB ID: 85361
PDB Deposition Date: 2010/6/28
Updated in MMDB: 2010/11
Experimental Method:
x-ray diffraction
Resolution: 2.18  Å
Source Organism:
Biological Unit for 3NPQ: monomeric; determined by author and by software (PISA)
Molecular Components in 3NPQ
Label Count Molecule
Nucleotide(1 molecule)
S-adenosylhomocysteine Riboswitch
Molecule annotation
Chemicals (6 molecules)
* Click molecule labels to explore molecular sequence information.

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