
(A) Structure of LacI as a homodimer (light and dark blue strands) with DNA (yellow strand). The N-terminal subdomain whose interface is important for DNA binding and the allosteric mechanism is at the upper part of the figure; the C-terminal domain is at the bottom. The 186 positions tolerant for six or more substitutions are colored in white on one monomer (Markiewicz et al. 1994; Suckow et al. 1996). For 31 of these positions, >50% of the substitutions were predicted to affect phenotype according to SIFT when experimentally they did not (see also Fig. 2, asterisks). These positions are shown as space-fill atoms in red. Noticeably, many of these occurred at the bottom face of the C-terminal domain. This structure is 1EFA from PDB (Bell and Lewis 2000). (B) Same figure rotated 90° about the Z-axis.











