Extended Data Fig. 1: Discovery of a ligandable cysteine in the JAK1/TYK2 pseudokinase domain.
From: Selective inhibitors of JAK1 targeting an isoform-restricted allosteric cysteine
a, Chemical structures of broadly reactive electrophilic fragments KB02 and KB05 evaluated previously for covalent reactivity with cysteines in the human T-cell proteome (Vinogradova, E. V. et al, Cell 182, 1009–1026 e29 (2020), b, Relative MS3 signal intensity values for all quantified IA-DTB-labeled, cysteine-containing peptides in TYK2 in KB02- or KB05-treated T cells compared to DMSO-treated T cells. The KB02- and KB05-liganded cysteine in TYK2 (C838) is highlighted in blue. Horizontal black bars indicate the median signal intensity for all other quantified TYK2 cysteines. Data are mean values combined from soluble and particulate proteomic of n = 2 (KB02) or n = 3 (KB05) independent replicates analyzed over 2 MS-ABPP experiments.
