S1 is an NAD-dependent ADP-ribosyltransferase, which plays a crucial role in the pathogenesis of B.pertussis causing disruption of normal host cellular regulation. It catalyzes the ADP-ribosylation of a cysteine in the alpha subunit of host heterotrimeric G proteins. In the absence of G proteins it also catalyzes the cleavage of NAD(+) into ADP-ribose and nicotinamide. It irreversibly uncouples the G-alpha GTP-binding proteins from their membrane receptors. Pertussis toxin contains five different chains, S1-S5. They are organized into 2 functional subunits: A, composed of S1 (which is toxic) and B, containing S2, S3, S5, and two copies of S4 (B binds to the membrane receptors). Dimers of S2-S4 and S3-S4 are held together by S5. The individual chains are secreted by a sec-dependent mechanism into the periplasm. Then, S1 associates with the outer membrane before it joins with the B subunit to form the secretion-competent holotoxin. The type IV secretion system ptl mediates secretion of assembled toxin through the outer membrane. Activated by the two-component regulatory system BvgS/BvgA. The region which spans amino acids 42-49 is required for enzymatic activity and contributes to the formation of a potentially important antigenic determinant. Currently used in vaccines available under the names Daptacel (Sanofi Pasteur), Infanrix (GlaxoSmithKline), Pediarix (GlaxoSmithKline), TriHIBit (Sanofi Pasteur) and Tripedia (Sanofi Pasteur). Thiol:disulfide oxidoreductases DsbA and DsbB are required for periplasmic toxin assembly, whereas DbsC is important for extracellular toxin secretion. Experiments with temporal expression of PTX indicate that holotoxin secretion is at a rate of 3 molecules/min/cell. Also, more of toxin chains S1, S2 and S3 are produced than secreted; one half of each chain is incorporated into holotoxin. Belongs to the bacterial exotoxin subunit A family.