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. 2022 Jul 21;18(11):1177–1183. doi: 10.1038/s41589-022-01065-9

Fig. 3. G12Si-1 binds covalently to Ser12 in the switch II pocket of K-Ras(G12S).

Fig. 3

a, Scheme of the nucleophilic ring opening of the β-lactone in G12Si-1 by serine 12. b, The X-ray co-crystal structure of the K-Ras(G12S)•GDP•G12Si-1 complex. 2Fo – Fc map for the ligand G12Si-1 and serine 12 is depicted in gray mesh (1.0σ). c, Crystal structure of the K-Ras(G12S)•GDP•G12Si-1 adduct and the K-Ras(G12C)•GDP•adagrasib adduct (PDB: 6USZ). d, Superimposition of the conformations of covalent ligands of the S-IIP: G12Si-1 (this work), adagrasib (PDB: 6USZ), sotorasib (PDB: 6OIM), ARS1620 (PDB: 5V9U). For X-ray crystallography data collection and refinement statistics, see Supplementary Table 1.