New insights into clostridial neurotoxin-SNARE interactions.
Botulinum neurotoxin serotype A (BoNT/A) has achieved a dichotomous status in modern medicine; it is both a versatile treatment for several neurological disorders and a lethal poison responsible for causing the neuroparalytic syndrome botulism. The extent of paralysis largely depends on the dosage of toxin received. The toxins block neurotransmitter release by delivering their Zn(2+)-dependent protease components to the presynaptic side of chemical synapses. These highly specialized enzymes exclusively hydrolyze peptide bonds within SNARE (soluble N-ethylmaleiamide-sensitive factor attachment protein receptor) proteins. Recently, the structural basis for the highly specific interaction between BoNT/A and its target SNARE, SNAP-25 (synaptosomal-associated protein of 25kDa), was elucidated. New details regarding the nature of the toxin-SNARE interactions could be exploited for novel inhibitor design.
Breidenbach
Mark A
MA
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA.
Brunger
Axel T
AT
D019274:Botulinum Toxins, Type A / Q000737:chemistry / Q000494:pharmacology*; D009465:Neuromuscular Agents / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors*; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000187:drug effects*
D009465:Neuromuscular Agents; D018377:Neurotransmitter Agents; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; D019274:Botulinum Toxins, Type A