Pertussis toxin subunit 1 (PTX-S1) (PTX-S1)

The Pertussis toxin S1 subunit is the catalytic 'A' component of the hexameric AB5-type exotoxin secreted by Bordetella pertussis, the causative agent of whooping cough. It functions as an ADP-ribosyltransferase that specifically targets the alpha subunits of inhibitory G-proteins, such as Gi and Go. By uncoupling these G-proteins from their associated receptors, the S1 subunit disrupts normal intracellular signaling, leading to an uncontrolled increase in cyclic AMP (cAMP) levels. This biochemical disruption is a primary driver of pertussis pathogenesis, contributing to impaired immune cell recruitment and the systemic lymphocytosis characteristic of the disease (Source: StatPearls, Pertussis). In clinical practice, the S1 subunit is the most critical antigen in acellular pertussis vaccines, where it is administered in a detoxified form (toxoid) to elicit a protective immune response. Beyond its role in vaccination, the S1 subunit is a target for experimental therapeutic monoclonal antibodies, such as hu1B7, which are designed to neutralize the toxin during active infection (Source: PMID: 32165466). Its ability to suppress early innate immune responses also makes it a key factor in the bacteria's ability to colonize the human respiratory tract.

Other names

Islet-activating protein S1 subunitPertussis toxin A protomerPtxAADP-ribosyltransferase subunit S1

The S1 subunit catalyzes the transfer of an ADP-ribose moiety from NAD+ to a conserved cysteine residue near the C-terminus of the alpha subunit of inhibitory heterotrimeric G-proteins (Gi, Go, and Gt). This covalent modification prevents the G-proteins from interacting with their cognate G protein-coupled receptors, effectively blocking inhibitory signals and leading to the constitutive activation of adenylate cyclase and pathologically increased intracellular cAMP levels (Source: UniProt P04977; PMID: 25100745).