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Scientists reveal structure of new botulism nerve toxin subtype
Date:12/22/2008

UPTON, NY Scientists at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory have determined the atomic-level structure of a third subtype of botulinum neurotoxin a deadly toxin produced by certain bacteria that causes the disease botulism, and is also used in cosmetic and therapeutic applications such as reducing wrinkles and calming a hyperactive bladder. The detailed structure, published online December 22, 2008, by the Journal of Molecular Biology, reveals a unique arrangement of the active components that may help explain why botulinum neruotoxin subtype E (one of seven distinct subtypes) is faster-acting than other subtypes previously studied at Brookhaven Lab and may have implications for improving vaccines and/or therapeutic agents.

"Understanding the differences among the seven botulinum neurotoxin subtypes is particularly imperative at a time of heightened concern about the potential use of these toxins as bioterror weapons," said Brookhaven biologist and lead author Subramanyam Swaminathan, who has conducted extensive research on botulinum neurotoxins supported by DOE, the U.S. Army, and the National Institutes of Health. Although experimental vaccines administered prior to exposure can inhibit the neurotoxin's destructive action, no effective pharmacological treatment exists.

All seven neurotoxin subtypes cause their deadly effects using a common mechanism, with each step being activated by a different portion, or domain, of the toxin protein. First the neurotoxin binds to a nerve cell; then it moves into the cell; and then it cleaves specific proteins that block the release of neurotransmitters, the chemicals nerve cells use to communicate with one another and with muscles. Without that communication, muscles, including those used to breathe, become paralyzed.

"Blocking any of these steps could thwart the toxins' deadly action," Swaminathan said. "But to do that, we need to understand the details
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Contact: Karen McNulty Walsh
kmcnulty@bnl.gov
631-344-8350
DOE/Brookhaven National Laboratory
Source:Eurekalert

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