Accession Number : ADA299496

Title :   Crystallographic Studies of the Anthrax Lethal Toxin.

Descriptive Note : Annual rept. 1 Jul 94-30 Jun 95,

Corporate Author : DANA-FARBER CANCER INST BOSTON MA

Personal Author(s) : Liddington, Robert C.

PDF Url : ADA299496

Report Date : 27 JUL 1995

Pagination or Media Count : 27

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.

Descriptors :   *LETHALITY, *ANTHRAX, *TOXINS AND ANTITOXINS, *VACCINES, *BACTERIAL TOXINS, *BACILLUS ANTHRACIS, FUNCTIONS, CRYSTAL STRUCTURE, HUMANS, BIOCHEMISTRY, PROTEINS, SPORES, MUTATIONS, USER NEEDS, THERAPY, DEATH, GENETICS, ANTIGENS, FRAGMENTS, RESIDUES, CRYSTALLOGRAPHY, ATOMIC STRUCTURE, INHALATION.

Subject Categories : Pharmacology
      Toxicology

Distribution Statement : APPROVED FOR PUBLIC RELEASE