Accession Number : ADA314005

Title :   Crystallographic Studies of the Anthrax Lethal Toxin.

Descriptive Note : Annual rept.,

Corporate Author : DANA-FARBER CANCER INST BOSTON MA

Personal Author(s) : Frederick, Christin A.

PDF Url : ADA314005

Report Date : JUL 1996

Pagination or Media Count : 30

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. In the previous report we described the first atomic resolution structure of PA, revealing that the molecule is composed largely of beta-sheets organized into four domains. This information can be used in the design. of recombinant PA vaccines. In this report we describe additional features of the full-length PA molecule derived from further crystallographic refinement and careful examination of the structure. We compare two crystal forms of PA grown at different pH values and discuss the functional implications. A complete definition of the function of each domain must await the crystal structure of the PA63 heptamer. We have grown crystals of the heptamer under both detergent and detergent-free conditions, and made substantial progress towards the crystal structure. The mechanism of anthrax intoxication in the light of our results is reviewed.

Descriptors :   *LETHALITY, *ANTHRAX, *ANTIGENS, *TOXINS AND ANTITOXINS, *CRYSTALLOGRAPHY, *INTOXICATION, *BACILLUS ANTHRACIS, CRYSTAL STRUCTURE, HUMANS, RESOLUTION, CRYSTALS, SPORES, USER NEEDS, DETERGENTS, VALUE, DEATH, REFINING, ATOMIC PROPERTIES, PH FACTOR, VACCINES, BACTERIAL TOXINS, ATOMIC STRUCTURE, INHALATION.

Subject Categories : Medicine and Medical Research
      Toxicology
      Microbiology
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE