Crystal structure of SNAP-25 in complex with botulinum neurotoxin and uses thereof

摘要

The present invention provides a crystallized form of the E224Q Y336F mutant of the light chain of botulinum neurotoxin serotype A (BoNT/A) protein as well as the atomic structure of this mutant protein. The present invention also provides crystals of the E224 Y336F mutant of the BoNT/A light chain in complex with the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) domain of the SNAP-25 (synaptosome-associated protein-25 kDa) protein as well as the atomic structure of this complex. The present invention further provides a method of determining whether an agent mimics a region of the SNAP-25 protein that interacts with BoNT/A. With this method, a three-dimensional representation of the SNAP-25 region is used to computationally compare the agent with the three-dimensional representation of the SNAP-25 region.