Computer-generated “ribbon” representations of the molecular structure of botulinum neruotoxin subtypes E (left) and B (right). The accompanying schematics show that in subtype E, both the binding domain (yellow) and the catalytic domain (red — which cleaves cellular proteins to block the release of neurotransmitters) lie on one side of the translocation domain (green). On subtype B, the binding and catalytic domains flank the central translocation domain. This structural difference may explain why subtype E is a faster-acting toxin. (Credit: Image courtesy of DOE/Brookhaven National Laboratory)
The current study of botulinum subtype E, also conducted at the NSLS, disproved that assumption, taking the scientists by surprise. Instead of the flanking arrangement, the binding and protein-cleaving domains of subtype E are both on the same side of the translocation domain. In addition, while all other subtypes are made of two protein chains, subtype E is a single-chain molecule.
For example, in the treatment of hyperactive bladder disorders, botulinum neurotoxin subtype A is currently used to inhibit neurotransmitter release and control bladder muscles. But it can take days or a week for the drug to be effective. A faster-acting neurotoxin might improve the response.