Fig. 23
From: PROTAC’ing oncoproteins: targeted protein degradation for cancer therapy
Crystal structure of VHL-compound 97-SMARCA2BD ternary complex (PDB 6HAX). The crystal structure depicts a sought after T-stacking interaction between the linker aryl group and VHLY98. VHLR69 forms critical interactions with the backbone of SMARCA2BD residues and a water-mediated hydrogen bond to the VHL ligand. VHLR69A mutations dramatically reduce degrader potency. Additional ligand-protein interactions are depicted. Image created using Schrödinger Bioluminate with PDB 6HAX. SMARCA2BD is depicted in cyan and VHL in brownish orange