4hev
Clostridium Botulinum Serotype A Light Chain Inhibited By Adamantane HydroxamateClostridium Botulinum Serotype A Light Chain Inhibited By Adamantane Hydroxamate
Template:ABSTRACT PUBMED 23340139
FunctionFunction
[BXA1_CLOBO] Inhibits acetylcholine release. The botulinum toxin binds with high affinity to peripheral neuronal presynaptic membrane to the secretory vesicle protein SV2. It binds directly to the largest luminal loop of SV2A, SV2B and SV2C. It is then internalized by receptor-mediated endocytosis. The C-terminus of the heavy chain (H) is responsible for the adherence of the toxin to the cell surface while the N-terminus mediates transport of the light chain from the endocytic vesicle to the cytosol. After translocation, the light chain (L) hydrolyzes the 197-Gln-|-Arg-198 bond in SNAP-25, thereby blocking neurotransmitter release. Inhibition of acetylcholine release results in flaccid paralysis, with frequent heart or respiratory failure.
About this StructureAbout this Structure
4hev is a 2 chain structure with sequence from Clostridium botulinum. Full crystallographic information is available from OCA.
ReferenceReference
- ↑ Silhar P, Silvaggi NR, Pellett S, Capkova K, Johnson EA, Allen KN, Janda KD. Evaluation of adamantane hydroxamates as botulinum neurotoxin inhibitors: synthesis, crystallography, modeling, kinetic and cellular based studies. Bioorg Med Chem. 2013 Mar 1;21(5):1344-8. doi: 10.1016/j.bmc.2012.12.001. Epub, 2012 Dec 20. PMID:23340139 doi:10.1016/j.bmc.2012.12.001