Figure 2: Crystal structure of the nucleotide exchange inhibitor DARPin K27 binding to K-Ras G12V at 3.2 Å resolution.
From: Structural and functional characterization of a DARPin which inhibits Ras nucleotide exchange
DARPin K27 is shown binding to the inactive form of K-Ras G12V, crystallized in the presence of GDP (a). Two views of the complex are shown, rotated at 90° about a vertical axis, with switch 1 and 2 regions annotated. Comparison of the Ras G12V/DARPin K27 complex with unbound Ras G12V structures in the GDP (PDB code: 4TQ9) and GTP analogue-bound (PDB code: 4EFM) states (b). Ras in the DARPin K27 complex (green) aligns well with unbound GDP Ras (blue) particularly in the switch 1 loop, whereas GTP analogue-bound Ras (orange) shows the expected conformational change in the switch 1 loop which predicts a clash with the phenylalanine sidechain at position 56 in K27 (see inset).
