BOTOX® (Botulinum
Toxin Type A) Purified Neurotoxin Complex is a 900-kilodalton (900-kD)
complex containing type A neurotoxin and associated proteins. There
are general structural and functional similarities among all 7 botulinum
neurotoxin types (A through G). All are synthesized as single-chain
polypeptides with molecular weights of approximately 150 kD. These single-chain
molecules are activated by proteolytic enzymes in a process referred
to as nicking or cleaving.1 Activation of botulinum toxin type A is achieved
by nicking or cleavage of the neurotoxin protein by endogenous bacterial
enzymes.
Once it is nicked or cleaved, the ~150-kD single-chain molecule forms
a dichain molecule consisting of an ~100-kD heavy chain linked by disulfide
bonding to an ~50-kD light chain. The heavy chain is responsible for
high-affinity docking of the neurotoxin to the presynaptic nerve terminal
receptor, enabling the internalization of the bound toxin into the cell.
The light chain is a zinc-dependent endopeptidase that cleaves membrane
proteins responsible for docking acetylcholine vesicles on the inner
side of the nerve terminal membrane.2,3 The cleavage of these proteins
precludes fusion of the vesicles with the nerve membrane, thereby preventing
release of neurotransmitters into the neuromuscular junction.4
1. Schantz EJ. Historical perspective. In: Jankovic J, Hallet M, eds.
Therapy With Botulinum Toxin. New York, NY: Marcel Dekker, Inc; 1994:xxiii-xxvi.
2. Coffield JA, Considine RV, Simpson LL. The site and mechanism of action
of botulinum neurotoxin. In: Jankovic J, Hallet M, eds. Therapy With Botulinum
Toxin. New York, NY: Marcel Dekker, Inc; 1994:3-13.
3. Data on file, Allergan, Inc., 1998.
4. Martin TFJ. Stages of regulated exocytosis. Trends Cell Biology. 1997;7:271-276.
