A5009484351- Botulinum Toxin and Related Neurological Disorders
- Hereditary Neurological Disorders
- Biochemical and Structural Characterization
University of California, Irvine
2020-2022
Abstract The botulinum neurotoxin serotype A (BoNT/A) cuts a single peptide bond in SNAP25, an activity used to treat wide range of diseases. Reengineering the substrate specificity BoNT/A’s protease domain (LC/A) could expand its therapeutic applications; however, LC/A’s extended recognition (≈ 60 residues) challenges conventional approaches. We report directed evolution method for retargeting LC/A and retaining exquisite specificity. resultant eight-mutation (omLC/A) has improved cleavage...
Abstract The botulinum neurotoxin serotype A (BoNT/A) cuts a single peptide bond in SNAP25, an activity used to treat wide range of diseases. Reengineering the substrate specificity BoNT/A’s protease domain (LC/A) could expand its therapeutic applications; however, LC/A’s extended recognition (≈60 residues) challenges conventional approaches. We report directed evolution method for retargeting and retaining exquisite specificity. resultant eight-mutation LC/A (omLC/A) has improved cleavage...