Wrestling with the anthrax toxin

The crystal structure of the oedema factor component of the anthrax toxin shows how it locks onto and disables a host signaling molecule.

Tudor Toma(

Oedema factor (EF) — a calmodulin-activated adenylyl cyclase — is important in the pathogenesis of anthrax, but the relationship between the structure of EF and its function remains unclear. In January 24 Nature, Chester Drum and colleagues from University of Chicago, show the structural basis for the activation mechanism of anthrax adenylyl cyclase exotoxin by calmodulin.

Drum et al. examined the X-ray structures of EF and found that four discrete regions form a surface that recognizes an extended conformation of calmodulin. On calmodulin binding, an EF helical domain of relative molecular mass 15,000 undergoes a 15 Å translation and a 30º rotation away from the EF catalytic core, which stabilizes a disordered loop and leads to enzyme activation (Nature 2002, 415:396-402). The calmodulin is subsequently unable to effectively regulate cellular cyclic AMP levels, with the result that the cell can no longer regulate its water...

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