Figure 3. Secondary structure computer modeling of WT and mutant proinsulins.

Shown are superimposed Cα traces of WT (blue) and all mutated insulins (purple), with the exception of L^B6V. The positions of disulfide bridges are also marked. None of the mutations caused substantial distortion of the secondary structure, with the exception of L^B15Y^B16delinsH (yellow trace at left), where an α-helical disruption is apparent (arrow). This was also evident in the superimposition of WT insulin and L^B15Y^B16delinsH. The L^B6P mutation alters the hydrophobic core of the protein. The L^B11P mutation affects the hydrophobic core of the protein. The C^A6Y mutation disrupts the A6–A11 disulfide bridge; the tyrosine is oriented inside the hydrophobic core of the protein, where it engages L^B6 in a stacking interaction. The hAkita mutation — used in this study as positive control — disrupts the B7–A7 disulfide bridge, and the tyrosine is solvent exposed.