eIF2B-catalyzed nucleotide exchange and phosphoregulation …
May 3, 2019 · We report cryo–electron microscopy structures of eIF2 bound to eIF2B in the dephosphorylated state. The structures reveal that the eIF2B decamer is a static platform upon which one or two flexible eIF2 trimers bind and align with eIF2B’s bipartite catalytic centers to catalyze nucleotide exchange.
A helical fulcrum in eIF2B coordinates allosteric regulation
Nov 9, 2023 · Using hydrogen–deuterium exchange–mass spectrometry and cryo-electron microscopy, we identified a central α-helix whose orientation allosterically coordinates eIF2B conformation and assembly....
Sean M. Healey & AMG Center Announces Topline Results in …
Mass General is recognized as a top hospital on the U.S. News & World Report Best Hospitals Honor Roll for 2024-2025. Conditions & Treatments . ... Sean M. Healey & AMG Center Announces Topline Results in HEALEY ALS Platform Trial with eIF2B Agonist DNL343 . Primary endpoint of overall function (ALSFRS-R) and survival, and key secondary ...
Denali Therapeutics Announces Topline Results for Regimen G …
Jan 6, 2025 · SOUTH SAN FRANCISCO, Calif., Jan. 06, 2025 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (NASDAQ: DNLI) today announced topline results from an analysis of Regimen G of the Phase 2/3 HEALEY ALS...
Denali Therapeutics Announces Initiation of Phase 1b Study of EIF2B …
Sep 9, 2021 · DNL343 is designed to activate EIF2B and thereby restore protein synthesis, disperse TDP-43 aggregates, and improve neuronal survival.
Structural basis for eIF2B inhibition in integrated stress response
May 3, 2019 · To elucidate how the eIF2 phosphorylation status regulates the eIF2B activity, we determined cryo–electron microscopic and crystallographic structures of eIF2B in complex with unphosphorylated or phosphorylated eIF2.
Calico Life Sciences Announces that Fosigotifator (ABBV-CLS …
Jun 7, 2024 · Calico and AbbVie are currently conducting a Phase 1b/2 trial of fosigotifator to evaluate the safety, tolerability, and pharmacokinetics of fosigotifator in participants diagnosed with VWM disease. This study is the first time an eIF2B activator has been administered to people with VWM disease.
Denali Therapeutics Announces Topline Results for Regimen G …
Jan 6, 2025 · SOUTH SAN FRANCISCO, Calif., Jan. 06, 2025 (GLOBE NEWSWIRE) — Denali Therapeutics Inc. DNLI today announced topline results from an analysis of Regimen G of the Phase 2/3 HEALEY ALS Platform Trial evaluating eIF2B agonist DNL343 in the treatment of amyotrophic lateral sclerosis (ALS).
eIF2B and the Integrated Stress Response: a structural and …
Here, we discuss the recent reports on the structure, function, and regulation of eIF2B; the pre-clinical data on the use of ISR inhibitors for treatment of neurodegenerative disorders; and how the new structural and biochemical information can inform and influence the use of eIF2B as a therapeutic target.
Regulation and function of elF2B in neurological and metabolic ...
Jun 30, 2022 · Here, current knowledge of the role of eIF2B in the ISR is discussed within the context of normal and disease states focusing particularly on diseases such as vanishing white matter disease (VWMD) and permanent neonatal diabetes mellitus (PNDM), which are directly linked to mutations in eIF2B.