Nature Communications (Dec 2020)
Activation of the IRE1 RNase through remodeling of the kinase front pocket by ATP-competitive ligands
- Elena Ferri,
- Adrien Le Thomas,
- Heidi Ackerly Wallweber,
- Eric S. Day,
- Benjamin T. Walters,
- Susan E. Kaufman,
- Marie-Gabrielle Braun,
- Kevin R. Clark,
- Maureen H. Beresini,
- Kyle Mortara,
- Yung-Chia A. Chen,
- Breanna Canter,
- Wilson Phung,
- Peter S. Liu,
- Alfred Lammens,
- Avi Ashkenazi,
- Joachim Rudolph,
- Weiru Wang
Affiliations
- Elena Ferri
- Structural Biology, Genentech, Inc., 1 DNA Way
- Adrien Le Thomas
- Cancer Immunology, Genentech, Inc., 1 DNA Way
- Heidi Ackerly Wallweber
- Structural Biology, Genentech, Inc., 1 DNA Way
- Eric S. Day
- Pharmaceutical Development, Genentech, Inc., 1 DNA Way
- Benjamin T. Walters
- Biochemical and Cellular Pharmacology, Genentech, Inc., 1 DNA Way
- Susan E. Kaufman
- Biochemical and Cellular Pharmacology, Genentech, Inc., 1 DNA Way
- Marie-Gabrielle Braun
- Discovery Chemistry, Genentech, Inc., 1 DNA Way
- Kevin R. Clark
- Biochemical and Cellular Pharmacology, Genentech, Inc., 1 DNA Way
- Maureen H. Beresini
- Biochemical and Cellular Pharmacology, Genentech, Inc., 1 DNA Way
- Kyle Mortara
- BioMolecular Resources, Genentech, Inc., 1 DNA Way
- Yung-Chia A. Chen
- Cancer Immunology, Genentech, Inc., 1 DNA Way
- Breanna Canter
- Discovery Chemistry, Genentech, Inc., 1 DNA Way
- Wilson Phung
- Microchemistry, Proteomics & Lipidomics, Genentech, Inc., 1 DNA Way
- Peter S. Liu
- Microchemistry, Proteomics & Lipidomics, Genentech, Inc., 1 DNA Way
- Alfred Lammens
- Proteros Biostructures GmbH
- Avi Ashkenazi
- Cancer Immunology, Genentech, Inc., 1 DNA Way
- Joachim Rudolph
- Discovery Chemistry, Genentech, Inc., 1 DNA Way
- Weiru Wang
- Structural Biology, Genentech, Inc., 1 DNA Way
- DOI
- https://doi.org/10.1038/s41467-020-19974-5
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 15
Abstract
The RNase activity of Inositol-Requiring Enzyme 1 (IRE1) can be allosterically regulated by ATP-competitive inhibitors of the IRE1 kinase domain. Here, the authors identify ATP-competitive IRE1 RNase activators with improved selectivity and cellular activity, and elucidate their mechanism of action.
