Clostridium botulinum neurotoxin serotype A light chain (BoNT/A-LC)

Clostridium botulinum neurotoxin serotype A light chain is the catalytically active 50 kDa N-terminal domain of the botulinum neurotoxin serotype A (BoNT/A), a highly potent bacterial toxin comprised of a disulfide-linked di-chain protein with a light and heavy chain. The light chain is a Zn(II)-dependent metalloprotease that specifically cleaves SNAP-25, a component of the SNARE complex required for the exocytosis of acetylcholine at neuromuscular junctions, thereby blocking neurotransmitter release and inducing flaccid paralysis. The BoNT/A light chain is the primary therapeutic and toxic agent of botulinum toxin activity. Due to its clinical and bioterrorism relevance, it is a major therapeutic target for the development of small-molecule inhibitors and antitoxins, with multiple crystal structures available complexed to candidate inhibitors that illustrate its conformational flexibility and active site morphology. The inhibition or modification of BoNT/A-LC is central to both botulism treatment and the refinement of BoNT-based therapeutics for neurological disorders.

Other names

botulinum neurotoxin type A light chainBoNT/A light chainLC/A

Inhibition of Zn(II)-dependent protease activity; prevention of SNAP-25 cleavage; blockade of acetylcholine release at neuromuscular junction