Zinc content of the Bacillus anthracis lethal factor.

We present evidence that the anthrax toxin lethal factor binds multiple zinc atoms. Results from atomic adsorption spectroscopy indicate that lethal factor contains approximately three zinc atoms per toxin molecule. Lethal factor treated with EDTA and o-phenanthroline contained a similar number of zinc atoms, indicating that all three zinc atoms are tightly bound to the protein. Lethal factor contains the highly conserved zinc-binding consensus sequence, HExxH, that is present in all known zinc metalloproteases. In addition, lethal factor contains an inverted form of this motif, HxxDH, which may also be involved in zinc binding. Using a large array of protease model substrates, however, we were unable to detect an endogenous protease activity for lethal factor.