Atomic-level insights into metabolite recognition and specificity of the SAM-II riboswitch.

Although S-adenosylhomocysteine (SAH), a metabolic by-product of S-adenosylmethionine (SAM), differs from SAM only by a single methyl group and an overall positive charge, SAH binds the SAM-II riboswitch with more than 1000-fold less affinity than SAM. Using atomistic molecular dynamics simulations, we investigated the molecular basis of such high selectivity in ligand recognition by SAM-II riboswitch. The biosynthesis of SAM exclusively generates the (S,S) stereoisomer, and (S,S)-SAM can spontaneously convert to the (R,S) form.

Atomistic basis for the on-off signaling mechanism in SAM-II riboswitch.

Many bacterial genes are controlled by metabolite sensing motifs known as riboswitches, normally located in the 5' un-translated region of their mRNAs. Small molecular metabolites bind to the aptamer domain of riboswitches with amazing specificity, modulating gene regulation in a feedback loop as a result of induced conformational changes in the expression platform. Here, we report the results of molecular dynamics simulation studies of the S-adenosylmethionine (SAM)-II riboswitch that is involved in regulating translation in sulfur metabolic pathways in bacteria.