Communications Biology (Mar 2021)
Engineering subtilisin proteases that specifically degrade active RAS
- Yingwei Chen,
- Eric A. Toth,
- Biao Ruan,
- Eun Jung Choi,
- Richard Simmerman,
- Yihong Chen,
- Yanan He,
- Ruixue Wang,
- Raquel Godoy-Ruiz,
- Harlan King,
- Gregory Custer,
- D. Travis Gallagher,
- David A. Rozak,
- Melani Solomon,
- Silvia Muro,
- David J. Weber,
- John Orban,
- Thomas R. Fuerst,
- Philip N. Bryan
Affiliations
- Yingwei Chen
- Potomac Affinity Proteins
- Eric A. Toth
- Institute for Bioscience and Biotechnology Research
- Biao Ruan
- Potomac Affinity Proteins
- Eun Jung Choi
- Potomac Affinity Proteins
- Richard Simmerman
- Potomac Affinity Proteins
- Yihong Chen
- Institute for Bioscience and Biotechnology Research
- Yanan He
- Institute for Bioscience and Biotechnology Research
- Ruixue Wang
- Institute for Bioscience and Biotechnology Research
- Raquel Godoy-Ruiz
- Institute for Bioscience and Biotechnology Research
- Harlan King
- Institute for Bioscience and Biotechnology Research
- Gregory Custer
- Institute for Bioscience and Biotechnology Research
- D. Travis Gallagher
- Institute for Bioscience and Biotechnology Research
- David A. Rozak
- Unified Culture Collection, United States Army Research Institute of Infectious Diseases
- Melani Solomon
- Institute for Bioscience and Biotechnology Research
- Silvia Muro
- Institute for Bioscience and Biotechnology Research
- David J. Weber
- Institute for Bioscience and Biotechnology Research
- John Orban
- Institute for Bioscience and Biotechnology Research
- Thomas R. Fuerst
- Institute for Bioscience and Biotechnology Research
- Philip N. Bryan
- Potomac Affinity Proteins
- DOI
- https://doi.org/10.1038/s42003-021-01818-7
- Journal volume & issue
-
Vol. 4,
no. 1
pp. 1 – 13
Abstract
Chen et al. describe a rational design of subtilisin mutants that degrade active RAS by cleaving a conserved sequence in switch 2. They further modified the active site to be dependent on a cofactor to generate high target specificity. Proteases engineered to cleave this region degraded RAS in vitro and in cells with a promise of adaptability for other target proteins too.
