Crystallographic Studies of the Anthrax Lethal Toxin.
Abstract
The lethal form of Anthrax results from the inhalation of anthrax spores. Death is primarily due to the effects of the lethal toxin (Protective Antigen (PA) + lethal Factor) from the causative agent, Bacillus anthracis. All the Anthrax vaccines currently in use or under development contain or produce PA, the major antigenic component of anthrax toxin, and there is a clear need for an improved vaccine for human use. The work described in this report defines for the first time the atomic resolution structure of PA, revealing the domain structure of the molecule and the precise residues involved in each of the four domains. Together with existing biochemical and genetic data, we have begun to assign functions to each domain, although some of these assignments must remain speculative until the crystal structure of the oligomeric from of the protein (PA63) has been determined. This information can be used in the construction of recombinant domain fragments and mutant proteins that lack many of the key functions of the parent protein, but are highly immunogenic and have improved therapeutic properties as vaccines.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 27, 1995
- Accession Number
- ADA299496
Entities
People
- Robert C. Liddington
Organizations
- Dana–Farber Cancer Institute