Active site-targeted covalent irreversible inhibitors of USP7 impair the functions of Foxp3+ T-regulatory cells by promoting ubiquitination of Tip60
Fig 3
NMR chemical shift perturbation analysis of P217564 binding to USP7core and mapping of the inhibitor-binding site.
(A) Inhibitor-induced chemical shift perturbations (Δω, Hz) plotted for each residue of USP7 core. Resonances that were detected in the free protein only but disappeared in the complex were arbitrarily set to 80 Hz. (B) USP7 core solvent accessible surface colored according to NMR chemical shift perturbation from (A) (pdb ID: 1NB8). The degree of magenta represents increased chemical shift changes induced by P217564 binding. USP7 core residues for which resonance assignments are missing in 1H-15N HSQC spectra are shown in light gold. Catalytic cysteine residue C223 is shown in red. The structure is shown in two orientations. The active site and the ubiquitin-binding “fingers” region are labeled.