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. Author manuscript; available in PMC: 2020 Dec 20.
Published in final edited form as: ACS Chem Biol. 2019 Oct 14;14(12):2595–2605. doi: 10.1021/acschembio.9b00482

Figure 2. Divergent Modulation of IRE1β’s RNase Domain with ATP-Competitive Inhibitors.

Figure 2.

A. Concentration regimes for testing the allosteric modulation of IRE1β*’s RNase domain. (top) Schematic of the oligomeric states of Low [IRE1β*] and High [IRE1β*]. (bottom) Real time fluorescence curves and initial rates for Low [IRE1β*] and High [IRE1β*]. Data shown are mean ± SEM, n=3. B. Activation of IRE1β*’s RNase activity. (top) Structure of the ATP-competitive RNase activator AT9283. (bottom) Real time fluorescence curves and rates of XBP1 mini-substrate cleavage for Low [IRE1β*] treated with DMSO (light gray) or AT9283 (purple) in the in vitro RNase assay. Data shown are mean ± SEM, n=3. C. Inhibition of IRE1β*’s RNase activity. (top) Structure of KIRA 1. (bottom) Real time fluorescence curves and rates of XBP1 mini-substrate cleavage for High [IRE1β*] treated with DMSO (dark gray) or 1 (coral) in the in vitro RNase assay. Data shown are mean ± SEM, n=3.