Clostridial neurotoxins: structure-function led design of new therapeutics.
The neurotoxins produced by various species of Clostridia are the causative agents of botulism and tetanus. The ability of the toxins, specifically those of the botulinum neurotoxin family, to disrupt neurotransmission has been exploited for use in several medical indications and now represents the therapeutic option of choice in a number of cases. Clostridial neurotoxins have been discovered to have a multi-domain structure that is shared between the various proteins of the family, and it has also been determined that each domain contributes a specific role to the holotoxin. The extensive use of recombinant expression approaches, along with solution of multiple crystallographic structures of individual domains, has enabled researchers to explore structurefunction relationships of the toxin domains more closely. These advances have facilitated a greater understanding of the potential use of individual domains for a wide variety of purposes, including the development of new therapeutics.
Chaddock
J A
JA
Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, Wiltshire SP40JG, United Kingdom. john.chaddock@hpa.org.uk
Marks
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PM
D018726:Anti-Dyskinesia Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001905:Botulinum Toxins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D015195:Drug Design; D008958:Models, Molecular; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
D018726:Anti-Dyskinesia Agents; D011993:Recombinant Fusion Proteins; D001905:Botulinum Toxins