Third Tine Of Anthrax's Toxic Trident

Following its recent publication of the structure of the first two toxins, this week's Nature (Vol. 415, No. 6870, 24 January 2002) contains a description of the structure of anthrax EF from Andrew Bohm at the Boston Medical Resarch Institute, Massachusetts, Wei-Jen Tang at the University of Chicago, Illinois, and colleagues.

The third tine of anthrax's toxic trident is harmless until it meets a crucial signalling molecule called calmodulin. The EF–calmodulin complex has a striking enzymatic activity, generating the important cellular signalling molecule cyclic AMP (cAMP). Normally, this is made by a designated cellular enzyme. EF has evolved to do the same job, only far more efficiently and through an entirely different mechanism. cAMP generation is thought to be important for the lethal effect of EF, so this difference provides hope that specific reagents can be developed to target EF and not essential cellular signalling pathways.

EF could also be a weak link, as its structure contains a deep, well defined molecular pocket that could represent an ideal target for future drugs. Bohm, Tang and colleagues "complete our atomic-resolution view of this toxic trinity", says Robert Liddington of the Burnham Institute in La Jolla, California, in an accompanying News and Views article.

CONTACT:

Andrew Bohm
tel +1 617 658 7767
e-mail bohm@bbri.org

Wei-Jen Tang
tel +1 773 702 4331
e-mail wtang@midway.uchicago.edu

Robert Liddington
tel +1 858 646 3136
e-mail rlidding@burnham-inst.org

(C) Naturepress release.

Message posted by: Trevor M. D'Souza