Figure 2
From: Discovery of Small Molecules that Inhibit the Disordered Protein, p27Kip1
Fragment hits show specific interactions with specific regions within the D2 subdomain of p27-KID.
Overlaid 2D 1H-15N “in-phase” HSQC NMR spectra showing chemical shift perturbations of specific residues within the D2 subdomain of p27-KID after titration of fragment hits SJ710 (a, Group 1) and SJ403 (d, Group 2). For each hit, a total of sixteen spectra were recorded. The concentration of 15N-p27-KID (100 μM) was kept constant throughout the titration and the concentration of the inhibitor was varied from 0 (red) to 3 mM (blue). All experiments were performed on a 800 MHz spectrometer and utilized acquisition parameters that provided a spectral resolution of 2.4 Hz and 1.7 Hz in the 1H and 15N dimensions, respectively. The insets in the lower left show resonances for the tryptophan indole NH moieties (s-W60, s-W76). (b,e) Expanded regions (blue box) showing a subset of the p27-KID residues involved in interaction with SJ710 (b) and SJ403 (e), respectively. (c,f) Expanded regions (black box) showing two of the p27-KID residues that do not show any perturbations upon interaction with SJ710 (c) and SJ403 (f), respectively.
