Reengineering the specificity of the highly selective Clostridium botulinum protease via directed evolution.
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ABSTRACT:
SUBMITTER: Dyer RP
PROVIDER: S-EPMC9200782 | biostudies-literature | 2022 Jun
REPOSITORIES: biostudies-literature
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Reengineering the specificity of the highly selective Clostridium botulinum protease via directed evolution.
Dyer Rebekah P RP Isoda Hariny M HM Salcedo Gabriela S GS Speciale Gaetano G Fletcher Madison H MH Le Linh Q LQ Liu Yi Y Brami-Cherrier Karen K Malik Shiazah Z SZ Vazquez-Cintron Edwin J EJ Chu Andrew C AC Rupp David C DC Jacky Birgitte P S BPS Nguyen Thu T M TTM Katz Benjamin B BB Steward Lance E LE Majumdar Sudipta S Brideau-Andersen Amy D AD Weiss Gregory A GA
Scientific reports 20220615 1
The botulinum neurotoxin serotype A (BoNT/A) cuts a single peptide bond in SNAP25, an activity used to treat a wide range of diseases. Reengineering the substrate specificity of BoNT/A's protease domain (LC/A) could expand its therapeutic applications; however, LC/A's extended substrate recognition (≈ 60 residues) challenges conventional approaches. We report a directed evolution method for retargeting LC/A and retaining its exquisite specificity. The resultant eight-mutation LC/A (omLC/A) has i ...[more]
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