The SMK box riboswitch, also known as SAM-III, is an RNA regulatory element that was found upstream of the methionine synthase metK genes in lactic acid bacteria from the Lactobacillales order of Firmicutes . This riboswitch is one of several riboswitches that recognize S-adenosylmethionine (SAM) as a ligand, and regulates the SAM synthase MetK . SAM is a common co-substrate involved in methyl group transfers and is synthesized from the methionine amino acid by MetK synthase. SAM binding to Smk box RNA causes a structural rearrangement that se-questers the ribosomal binding site, thus the S mk box riboswitch inhibits translation of the metK gene .
The x-ray crystal structure of the Smk box riboswitch from Enterococcus faecalis complexed with SAM was solved [18806797
]. This structure reveals that the most conserved nucleotides involved in SAM binding were organized around a junction between three helices. Other known SAM-binding riboswitches (e.g. SAM-I, SAM-II) do not share any apparent structural resemblance to Smk box riboswitch.