The SAM riboswitch, also known as S-box, is a highly conserved RNA structure that is involved in regulation of methionine and cysteine metabolism in Bacteria. S-box serves as a riboswitch that binds directly to S-adenosylmethionine (SAM) to regulate gene expression via attenuation of transcription using formation of alternative secondary structures in the S-box region [10094622, 12702767, 12910260]. SAM is a common co-substrate involved in methyl group transfers and is synthesized from the methionine amino acid by the SAM synthase MetK. The alignment of 100 S-box leaders confirms high degree of conservation of the S-box primary and secondary structure [15215334]. more

The S-box consists of five conserved helices, and single-stranded regions, and a pseudoknot structure formed by pairing between the end loop of helix P3 and the interior loop between helices P4 and P5 (Fig. 5). The solved x-ray crystal structure of the SAM riboswitch complexed with SAM has confirmed the predicted secondary structure of riboswitch and showed the four-way junction organization, with two sets of coaxially stacked helices arranged side-by-side and a pseudoknot formed between a stem loop and the a helix joining region [16810258, 18205390]. Search for S-boxes and analysis of operon structures identified a large number of new candidate methionine-regulated genes in various bacteria, mostly Firmicutes [15215334]. In the genomic search for new methionine-regulated genes, several new types of candidate methionine transporters including MetT amd MtsABC were identified [15215334].