Fig. 6: Inhibitor binds at the aromatic cage of the Tudor domain.
From: Pharmacological perturbation of the phase-separating protein SMNDC1
a Chemical shift perturbations (CSP) of Tudor domains SMNDC1 (red) and SMN (blue) in presence of 0.8 mM compound 13. Residues forming the aromatic cage are highlighted in bold. Left inlet shows cartoon representation of SMNDC1 in complex with compound 13 (light-brown sticks) calculated using semi-rigid body docking of compound 13 based on 23 intermolecular NOE restraints (see d and Supplementary Table 3). CSP per residue in presence of 8 mM compound 13 are displayed in cyan to red shades. Right inlet shows compound 13 with numbers indicating the assignment used in d and Supplementary Table 3. b Zoomed view of the binding site with residues forming the aromatic cage shown as sticks. Stacking contacts between the thiazole moiety of compound 13 and tryptophan 83 or tyrosine 111 indicated with dashed lines. c Overlay of 1H,15N-HSQC spectra of SMNDC1 in the presence of 0, 0.05, 0.15, 0.25, 0.5, 0.8, and 8 mM compound 13. Zoomed view shows residues in and near the aromatic cages. d Section of an in ω1-13C-filtered NOESY spectrum shows crosspeaks between inhibitor protons (red arrows) and aromatic cage protons (black) arrows. The crossing points of the dashed cyan lines indicate the locations of the intermolecular NOEs.
