With the recent world events and biological attacks within the United States, the issue of pathways involved in biological weapons has come to the forefront. One of the most potent and well known biological agents, Anthrax, is of increased concern. With the recent crystallization of the Lethal Factor (LF) (Pannifer et all. 2001) the mechanism of anthrax toxicity is slowly being discovered. Although there are antibiotics and vaccinations for the Anthrax, the mechanism of the toxin was not known. It was known that the lethal toxin (LeTx) of Anthrax is composed of two separate binding domains: The first is the protective antigen (PA), which binds to the target cell; The second is the lethal factor (LF) which is responsible for interfering with the Mitogen Activated Protein kinase cascading (MAPK) pathway (Vitale et all, 2000). The exact mechanism is not known, but this recent crystallization has led to the discovery of Mitogen-Activated Protein Kinase kinase's (MAPK kinase/ MAPKK) involvement in the pathway. MAPK's are signaling proteins that are involved in many aspects of cell life ranging from cell proliferation, responding to growth factors, insulin signaling, response to osmotic shock, UV radiation, cytotoxic chemicals; to name but a few(Lecture notes). It is this MAPK signaling cascade with which the LF attacks. Specifically, LF attacks the second stage of the MAPK cascade, which is the MAPKK. In my paper I will discuss the new discoveries of the toxin, the pathways involved/infected, the structures, and the significance of these findings.

Author: Mark Anderson

The University of Arizona

Biochemistry 462B- Honors Web Project

Dr. Elizabeth Vierling and Dr. Don Borque, Instructors