Negatively regulates glucose metabolism by binding directly to the promoter region of the kgu and gad operons (PubMed:22844393, PubMed:24019239). It also negatively regulates its own synthesis (PubMed:10438759, PubMed:10894751, PubMed:22844393). In addition, in pathogenic strains, PtxS modulates PtxR activity in response to 2-ketogluconate (PubMed:9645431, PubMed:22844393, PubMed:24019239). In the presence of PtxR, which also binds to the kgu and gad promoter regions, PtxS and PtxR form a tight complex, creating a DNA-loop that prevents RNA polymerase promoter access and expression of the glucose metabolism genes (PubMed:10931350, PubMed:22844393, PubMed:24019239). Binding of the 2-ketogluconate effector to PtxS causes PtxS/PtxR complex dissociation and leads to the dissolution of the repression DNA-loop, facilitating the entry of the RNA polymerase and enabling the transcription of the genes (PubMed:22844393, PubMed:24019239). Also plays an important role in the regulation of the expression of the virulence factor exotoxin A (toxA) (PubMed:9645431, PubMed:22844393). PtxS does not bind directly to the toxA promoter but negatively regulates the production of exotoxin A by binding to PtxR and interfering with its positive regulator activity (PubMed:9645431, PubMed:22844393). In the presence of 2-ketogluconate, PtxS is released and PtxR can recruit RNA polymerase (PubMed:22844393). 2-ketogluconate acts as a molecular effector and causes dissociation of the PtxS/PtxR complex. Interacts with PtxR in the absence of 2-ketogluconate (PubMed:22844393, PubMed:24019239). Binding of the 2-ketogluconate effector to PtxS causes PtxS/PtxR complex dissociation (PubMed:22844393, PubMed:24019239). Expression is enhanced by the global regulator MvaT, which binds to the ptxR-ptxS intergenic region (PubMed:15528665). Negatively autoregulates its own synthesis by binding to a specific operator site within the ptxS upstream region (PubMed:10438759, PubMed:10894751, PubMed:22844393). Contains an N-terminal helix-turn-helix DNA-binding domain and a C-terminal domain that binds the effector. Mutant exhibits a twofold increase in exotoxin A production.