3qiy
Crystal Structure of BoNT/A LC complexed with Hydroxamate-based Inhibitor PT-1Crystal Structure of BoNT/A LC complexed with Hydroxamate-based Inhibitor PT-1
Template:ABSTRACT PUBMED 21434688
FunctionFunction
[BXA1_CLOBH] 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
3qiy is a 1 chain structure with sequence from Clostridium botulinum. Full crystallographic information is available from OCA.
ReferenceReference
- ↑ Thompson AA, Jiao GS, Kim S, Thai A, Cregar-Hernandez L, Margosiak SA, Johnson AT, Han GW, O'Malley S, Stevens RC. Structural Characterization of Three Novel Hydroxamate-based Zinc Chelating Inhibitors of the C. botulinum Serotype A Neurotoxin Light Chain Metalloprotease Reveals a Compact Binding Site Resulting from 60/70 Loop Flexibility. Biochemistry. 2011 Mar 24. PMID:21434688 doi:10.1021/bi2001483