Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Hydrolase
Reexamination Certificate
2006-03-29
2009-06-30
Noakes, Suzanne M. (Department: 1656)
Chemistry: molecular biology and microbiology
Enzyme , proenzyme; compositions thereof; process for...
Hydrolase
C703S002000
Reexamination Certificate
active
07553651
ABSTRACT:
The present invention provides a crystallized form of the E223Q Y365F 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 E223Q Y365F 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.
REFERENCES:
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Giege et al. (1994) Acta Cryst., D50, 339-350.
Branden et al (1999) Introduction to Protein Structure, Second Edition, Garland Publishing Inc., New York, pp. 374-375 and 382.
Drenth (1995) Principles of X-ray Crystallography, Springer, New York, p. 1.
Kierzek et al. (2001) Biophys Chem, 91:1-20.
Wiencek (1999) Ann Rev Biomed Eng., 1:505-534.
Breidenbach et al., Substrate recognition strategy for botulinum neurotoxin serotype A., Dec. 16, 2004, Nature, vol. 432, pp. 925-929.
Breidenbach Mark A.
Brunger Axel T.
Board of Trustees of the Leland Stanford Junior University
Kim Alexander D
Noakes Suzanne M.
Thomas Kayden Horstemeyer & Risley LLP
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