Regulatory mechanism of ThDP riboswitches and the structure of ThDP and Pyrithiamin diphosphate. (Top) When ThDP is at lower concentration during the synthesis of the 5'-UTR, the ThDP riboswitch would not inhibit the expression of ThDP biosynthetic genes (a, b, c, left), then “gene on”. When ThDP is at higher concentration, depending on the the expression platform, the ThDP riboswitch would fold to a transcription terminator (a), a suppressor of translation initiation (b), or a modulator of splicing (c), it is the “gene off” state (a, b, c, right). (Bottom) The structure of ThDP and pyrithiamin diphosphate. The initiation codon and Shine-Dalgarno (SD) sequence are shaded green brown, complementary sequences and their alternate base pairing are shown in green. The red and blue represent ThDP and Mg2+ ions, respectively. This figure is modified from 76, 79.