Sandbox Reserved 966

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This Sandbox is Reserved from 15/11/2014, through 15/05/2015 for use in the course "Biomolecule" taught by Bruno Kieffer at the Strasbourg University. This reservation includes Sandbox Reserved 951 through Sandbox Reserved 975.

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Structure of the "Clostridium botulinum" neurotoxin serotype A light chain with Zn2+ cofactor bound

The Clostridium botulinum neurotoxin produced by the bacteria Clostridium botulinum (and some strains of Clostridium butyricium and Clostridium baratii) is the most lethal toxin known today. Seven serotypically botulinum neurotoxins (BoNTs) have been found, each of them is categorized into subtypes depending on their amino acid sequence. The protein is initially synthesized as a single polypeptide chain of ≈150 kDa and is then cleaved by a protease to yield the mature toxin, which consists of a light chain (LC which is 50 kDa) and a heavy chain (HC which is 100 kDa). LC and HC are held together by a long peptide belt, non-covalent interactions and a single inter-chain disulphide bond ^[1]

The "Clostridium botulinum" neurotoxin serotype A light chain (BoNT/A-LC) shown below is composed of 425 residues. It was obtained with high resolution X-ray crystal structure using an inhibitory peptide and the catalytic Zn(II) ion. ^[2]

1 Structure
- 1.1 Global aspect
- 1.2 Structural highlights
2 Mechanism
3 Therapeutic applications

Structure

Global aspect

BoNT/A-LC presents

Structural highlights

Mechanism

Therapeutic applications

In the late 1960s, a Edward Schantz and a San Francisco opthalmologist, Alan Scott, start to work on the using of the botulinum toxin in therapeutic process. First, they try to treat strabismus and in the late 1970s the neurotoxin is used in many therapeutic applications.

hyperhidrosis

We can now treat excessive sweating with botulinium toxin thanks to his action on the receptors of the parasympathetic network. Excessive dribbling can be treated in the same way.

Cosmetic

Non-lethal amount of botulinum toxin can be injected localy to paralyse targeted muscles and reduce wrinkles temporaly (5 to 6 months).

Blepharospesm and strabismus

Torticollis

UMN syndrome

Chronic migraine

Cervical dystonia

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@@ Line 21: / Line 21: @@
 We can now treat excessive sweating with botulinium toxin thanks to his action on the receptors of the parasympathetic network. Excessive dribbling can be treated in the same way.
 === Cosmetic ===
+Non-lethal amount of botulinum toxin can be injected localy to paralyse targeted muscles and reduce wrinkles temporaly (5 to 6 months).
 === Blepharospesm and strabismus ===
 === Torticollis ===