Researchers show how botulism toxin ensnares ...( ould compete with the toxin for an exos...)

ould compete with the toxin for an exosite and disrupt the protease's ability to attack its target," he said. "Such a drug would act instantaneously once it crossed into the cell. And it would not interfere with other essential similar proteases in the cell, because it wouldn't be attacking the active site of the enzyme itself."

While this kind of drug could prove useful in treating late-stage botulism or tetanus, noted Brunger, effective antibiotics and vaccines already exist to treat the diseases in most cases, if they are caught early.

In further studies, the researchers will extend their analysis to tetanus toxins, and to the other types of botulinum toxins. Such studies, he said, could reveal differences in how the toxins recognize their targets.

"These bacteria have developed very clever enzymatic machines for recognizing proteins, and it may be possible, given our structural knowledge, to modify these proteases for clinical use," Brunger said. "An intriguing possibility would be to use their specificity as the basis for enzymes engineered to attack proteins involved in disease."

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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
12-Dec-2004

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