Extended Data Fig. 2: Structure-activity relationship (SAR) studies to optimize the peptide inhibitor for a higher potency and lower molecular weight.
From: Complex-specific inhibitors for interrogating ATAC histone acetyltransferase complex
a, Histogram showing the inhibitory effects of decapeptides with various aromatic acyl groups. The red ones are the benzofuran derivatives. b.The overall structure of YEATS2 YEATS bound to H3K27bz in ribbon view. c, Illustration of the sequence of compound LS-74 to LS-77. d, In-gel fluorescence and competition curves of LS-74 to LS-77 against YEATS2 YEATS obtained from competitive photo-cross-linking assay. n = 2 independently biological replicates. e, Heatmap showing the inhibitory effects of compound LS-78 - LS-145 toward YEATS2 YEATS. f, Superimposition of the aromatic ‘sandwich’ cage in LS-131(Kbf), H3K27bz, H3K27cr in complex with YEATS2 YEATS. g, Sequence and structural alignments of reader pocket loops among four human YEATS domains. Steel blue, YEATS2 YEATS; Light gray, AF9 YEATS (PDB ID: 5HJB); Orange, ENL YEATS (PDB: 5J9S); Light pink, GAS41 YEATS (PDB ID: 5XTZ). h, Structural overlay of YEATS domains. The ligand Kbf (green) was from PDB ID: 9PKU. Red arrowheads indicate a wide-end opening of YEATS.
