The C-terminal substrate binding domain of LysR-type transcriptional regulator Cbl, which is required for expression of sulfate starvation-inducible (ssi) genes, contains the type 2 periplasmic binding fold.Cbl is a member of the LysR transcriptional regulators that comprise the largest family of prokaryotic transcription factor. Cbl shows high sequence similarity to CysB, the LysR-type transcriptional activator of genes involved in sulfate and thiosulfate transport, sulfate reduction, and cysteine synthesis. In Escherichia coli, the function of Cbl is required for expression of sulfate starvation-inducible (ssi) genes, coupled with the biosynthesis of cysteine from the organic sulfur sources (sulfonates). The ssi genes include the ssuEADCB and tauABCD operons encoding uptake systems for organosulfur compounds, aliphatic sulfonates, and taurine. The genes in these operons encode an ABC-type transport system required for uptake of aliphatic sulfonates and a desulfonation enzyme. Both Cbl and CysB require expression of the tau and ssu genes. Like many other members of the LTTR family, the Cbl is composed of two functional domains joined by a linker helix involved in oligomerization: an N-terminal HTH (helix-turn-helix) domain, which is responsible for the DNA-binding specificity, and a C-terminal substrate-binding domain, which is structurally homologous to the type 2 periplasmic binding proteins. As also observed in the periplasmic binding proteins, the C-terminal domain of the bacterial transcriptional repressor undergoes a conformational change upon substrate binding which in turn changes the DNA binding affinity of the repressor. The structural topology of this substrate-binding domain is most similar to that of the type 2 periplasmic binding proteins (PBP2), which are responsible for the uptake of a variety of substrates such as phosphate, sulfate, polysaccharides, lysine/arginine/ornithine, and histidine. The PBP2 bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis.