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. 2020 Feb 11;117(7):3365–3367. doi: 10.1073/pnas.1921236117

Fig. 1.

Fig. 1.

KRAS dimers and biophysical validation. (A) KRAS G12D modeled dimer with BI-2852 (Protein Data Bank [PDB] ID code 6GJ8). The dimer interface was generated with symmetry operations from the published structure, showing a β-sandwich interface. (B) Cocrystal structure of KRAS G12D with compound 2 showing a similar β-sandwich interface as with BI-2852. (C) Published dimeric KRAS-G12D apo system (PDB ID code 6QUU) with an extended β-sheet interface. (D) Structure of compound 2 soaked in published KRAS-G12D soaking system. The compound needs to adapt to the extended β-sheet interface. (E) Isothermal titration calorimetry experiments with compound 2 showing binding to KRAS-G12D. (F) 2FoFc density around cocrystallized compound 2 at 1.57-Å resolution showing unambiguous binding. The interacting amino acids of both KRAS monomers are labeled. (G) 2FoFc density around compound 2 soaked in KRAS G12D at 1.9-Å resolution showing unambiguous binding of the ligand. The interacting amino acids of both KRAS monomers are labeled, respectively.