The SAM-SAH riboswitch was identified by bioinformatics as a conserved RNA-like structure located upstream of the methionine synthase metK genes in the order of Rhodobacterales of Alphaproteobacteria [20230605]. The SAM-SAH riboswitch was shown to bind directly both to S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) [20230605]. SAM is a common co-substrate involved in methyl group transfers, while SAH is a product of the SAM-dependent methylation reaction. The binding affinities for both compounds are similar, but binding for SAH is at least somewhat stronger. The intracellular balance of the two species has to be closely monitored to maintain cellular homeostasis and avoid toxicity [6760211]. more

Since the cellular concentration of SAM is higher than SAH, the SAM-SAH riboswitch more likely functions as SAM-sensing regulator of SAM biosynthesis. SAM-SAH riboswitches do not share any apparent structural resemblance to known riboswitches that bind SAM or SAH.